Podcasts about autosomal

In this episode of the Research Like a Pro Genealogy podcast, Nicole and Diana discuss the importance of research planning in genealogy and how AI tools can be used to assist in this process. They emphasize that a thorough research plan helps genealogists stay focused on their objectives, pick up where they left off if their work is interrupted, and approach problems systematically.  The hosts break down the elements of a research plan, which include the objective, a summary of known facts, a working hypothesis, identified sources, and a prioritized research strategy. They use the case study of researching Isabella Weatherford in Texas in the mid-1800s to illustrate these elements. Diana shares how she used AI tools to transcribe and organize a 57-page widow's pension file for Isabella, create a summary of known facts, and generate a hypothesis. They compare Diana's hypothesis with one generated by AI, highlighting the strengths and weaknesses of each.  The hosts also discuss how AI can be used to identify potential sources and prioritize research strategies. They emphasize the importance of verifying AI-generated information against reliable sources and using AI to generate new ideas and perspectives. This summary was generated by Google Gemini. Links Using AI in Research Planning: Isabella Weatherford Project Part 4 - https://familylocket.com/using-ai-in-research-planning-isabella-weatherford-project-part-4/ The Complete Guide to FamilyTreeDNA. Y-DNA, Mitochondrial, Autosomal and X-DNA by Roberta Estes - https://amzn.to/3TdS3IW (affiliate link to Amazon) Collaborate with Claude on Projects - https://www.anthropic.com/news/projects RLP 320: Using AI to Find Research Questions and Write Objectives - https://familylocket.com/rlp-320-using-ai-to-find-research-questions-and-write-objectives/ Sponsor – Newspapers.com For listeners of this podcast, Newspapers.com is offering new subscribers 20% off a Publisher Extra subscription so you can start exploring today. Just use the code “FamilyLocket” at checkout.  Research Like a Pro Resources Airtable Universe - Nicole's Airtable Templates - https://www.airtable.com/universe/creator/usrsBSDhwHyLNnP4O/nicole-dyer Airtable Research Logs Quick Reference - by Nicole Dyer - https://familylocket.com/product-tag/airtable/ Research Like a Pro: A Genealogist's Guide book by Diana Elder with Nicole Dyer on Amazon.com - https://amzn.to/2x0ku3d 14-Day Research Like a Pro Challenge Workbook - digital - https://familylocket.com/product/14-day-research-like-a-pro-challenge-workbook-digital-only/ and spiral bound - https://familylocket.com/product/14-day-research-like-a-pro-challenge-workbook-spiral-bound/ Research Like a Pro Webinar Series 2024 - monthly case study webinars including documentary evidence and many with DNA evidence - https://familylocket.com/product/research-like-a-pro-webinar-series-2024/ Research Like a Pro eCourse - independent study course -  https://familylocket.com/product/research-like-a-pro-e-course/ RLP Study Group - upcoming group and email notification list - https://familylocket.com/services/research-like-a-pro-study-group/ Research Like a Pro with DNA Resources Research Like a Pro with DNA: A Genealogist's Guide to Finding and Confirming Ancestors with DNA Evidence book by Diana Elder, Nicole Dyer, and Robin Wirthlin - https://amzn.to/3gn0hKx Research Like a Pro with DNA eCourse - independent study course -  https://familylocket.com/product/research-like-a-pro-with-dna-ecourse/ RLP with DNA Study Group - upcoming group and email notification list - https://familylocket.com/services/research-like-a-pro-with-dna-study-group/ Thank you Thanks for listening! We hope that you will share your thoughts about our podcast and help us out by doing the following: Write a review on iTunes or Apple Podcasts. If you leave a review, we will read it on the podcast and answer any questions that you bring up in your review. Thank you! Leave a comment in the comment or question in the comment section below. Share the episode on Twitter, Facebook, or Pinterest. Subscribe on iTunes, Stitcher, Google Podcasts, or your favorite podcast app. Sign up for our newsletter to receive notifications of new episodes - https://familylocket.com/sign-up/ Check out this list of genealogy podcasts from Feedspot: Top 20 Genealogy Podcasts - https://blog.feedspot.com/genealogy_podcasts/

Listen as Dr. London Smith (.com) and his producer Cameron discuss Autosomal Recessive Polycystic Kidney Disease with special guest Skunky Maltodextress (Victor Olivas). Not so boring! https://www.patreon.com/join/jockdocpodcast Hosts: London Smith, Cameron Clark. Guest: Victor Olivas. Produced by: Dylan Walker Created by: London Smith

Listen as Dr. London Smith (.com) and his producer Cameron discuss Autosomal Dominant Polycystic Kidney Disease with special guest Dr. Liverpool Smythe (Jennifer Prescott). Not so boring! https://www.patreon.com/join/jockdocpodcast Hosts: London Smith, Cameron Clark. Guest: Jennifer Prescott. Produced by: Dylan Walker Created by: London Smith

Do you know how far back you can go in your family tree and still use Autosomal DNA to find matches?   In this episode we explain what Autosomal DNA is, and then how to best use it to find matches in your family tree.    Want to hire a professional genealogist to assist with your family history research? Contact Legacy Tree Genealogists by visiting

While collectively uncommon, the clinical presentation of genetically-mediated spinal cord disorders frequently overlaps with other neurologic conditions. Our understanding of these disorders has grown considerably. In this episode, Kait Nevel, MD, speaks with Kara Stavros, MD, FAAN, author of the article “Genetic Myelopathies,” in the Continuum February 2024 Spinal Cord Disorders issue. Dr. Nevel is a Continuum® Audio interviewer and a neurologist and neuro-oncologist at Indiana University School of Medicine in Indianapolis, Indiana. Dr. Stavros is an associate professor of neurology and clinician educator at Warren Alpert Medical School of Brown University in Providence, Rhode Island. Additional Resources Read the article: Genetic Myelopathies Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @IUneurodocmom Guest: @StavrosKara Transcript  Full transcript available on Libsyn Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal, from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast of the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by clicking on the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the episode notes. AAN members, stay tuned after the episode to hear how you can get CME for listening. Dr Nevel: This is Dr Kait Nevel. Today, I'm interviewing Dr Kara Stavros on genetic myelopathies, which is part of the February 2024 Continuum issue on spinal cord disorders. Dr Stavros is an Associate Professor of Neurology and Clinician Educator at Warren Alpert Medical School at Brown University in Providence, Rhode Island. Welcome to the podcast. What is the biggest takeaway from your article that you'd like the neurologists listening to this to know? Dr Stavros: I would have to say that there's maybe two big takeaways that I would want to highlight. One would be that, generally speaking, in a nutshell, the genetic myelopathies can present with chronic and progressive symptoms, oftentimes (but not always) a family history of similar symptoms, and involvement of other structures outside of the spinal cord. Exclusion of the more treatable causes of myelopathy is a really key and important step in the diagnostic process. And because there are many different causes of genetic myelopathies, in some cases, the symptoms can overlap. I think this really underscores the utility of doing genetic testing to really confirm the precise underlying neurologic condition. The second takeaway that I would want to highlight is that, while treatment for most of these conditions is typically supportive, there have been a number of recent therapeutic breakthroughs for treatments in ALS, spinal muscular atrophy, adrenal myeloneuropathy, and Friedreich ataxia. While these aren't cures, it's really exciting and gratifying to see new therapeutics emerge via different mechanisms for patients with conditions that we've had very little treatment options for in the past. Dr Nevel: Yeah, I really enjoyed reading that in your article - about these treatments that have been coming out over the past several years. The one with Friedreich's ataxia, too - that looked like it was really just recently approved this year. Dr Stavros: Yes. Dr Nevel: And so, kind of jumping off of that topic - there have been these exciting treatments that have been coming through. What do you think is going to be the next big thing? Or what do you think is the next thing that might come through? Or what's going on in research in genetic myelopathies that might help our patients? Dr Stavros: That's a really great question. I think that, as far as the future in this area, genetic testing has definitely grown in terms of being able to identify more genes now that are implicated in these disorders than ever before. But this is still an area where our knowledge is continuing to evolve. So, I think the future holds further advancements in our ability to successfully diagnose patients who have these conditions and provide them with the sense of closure that having a definitive diagnosis brings, as well as opening the door to potentially targeted treatment options once a specific diagnosis is made. Another thing I think the future holds is continued development of expanded treatment options for patients with these conditions, both in terms of advancing our supportive care capabilities and then also providing more disease-modifying therapies. Again, as I mentioned, in recent years, new disease-modifying treatments have actually become available for several of these conditions. And I think that's just the beginning. There's going to be more to come, for sure. Dr. Nevel: Yeah, that would be great. Going back to the genetic testing and how things are - we're finding more and more and more genes. When you decide that genetic testing is indicated, how do you counsel your patients about genetic testing and walk them through that process? Dr Stavros: Okay - I would say that it usually starts with having a conversation with the patient about whether they want to pursue genetic testing or not for the particular condition or conditions that are suspected. Genetic testing is really helpful to, again, confirm the diagnosis once the initial diagnostic workup perhaps has given you some clues as to what the underlying condition might be. Again, because sometimes the clinical symptoms can overlap in different genetic myelopathies in particular, the genetic diagnosis can be really important as far as getting a definitive, final diagnosis. Usually testing is pretty carefully considered and the risks versus the benefits are explored with the patient. Oftentimes, this is done in conjunction with a genetic counselor or with genetics clinic. So, there's a lot of teamwork there in working with the genetics department, at least in my experience. There's a lot of options that might include testing a panel of genes for the suspected condition, to up to whole-exome sequencing. Again, this is really like an evolving landscape. So, we have a current understanding of the genes that are implicated in some of the genetic myelopathies, but there's still so much that we don't know. So, a lot of times, testing can result inconclusive or may be falsely negative, and it can be tough because a negative test doesn't necessarily exclude a potential genetic etiology. It becomes a very nuanced, I think, conversation and journey with the patient. Dr Nevel: Yeah, and in your article you mentioned some of the health care disparities that exist around genetic testing and access to genetic testing, specifically. How do we, as clinicians, try to mitigate inequities in regard to access, or in regards to being able to offer our patients genetic testing - is there anything that we can do? Dr Stavros: I do think there are some resources available, where free or sponsored testing can be utilized from nonprofit organizations or pharmaceutical companies. But you're right that this is a real area for potential health care disparities. And making sure that we have equitable access to genetic testing is really important. Some of the issues that come up are: limited access due to location; due to socioeconomic factors; a lack of awareness on the part of the patient or sometimes the provider about testing that's available; cost, of course, being a big issue, oftentimes; and sometimes, distrust of how the medical information, the genetic information, might be used or protected. Dr Nevel: What do you think is one of the most challenging things about managing patients with genetic myelopathies? Dr Stavros: I think one of the more challenging aspects of the care is the diagnostic journey. I think that some of these conditions - most of them are not terribly common – and they may not always be at the top of our differential diagnosis in the course of a workup for myelopathy. The first step, I think, is really continuing to be aware of these conditions and not letting them become a “blind spot” when we're formulating a differential diagnosis for a patient with myelopathic symptoms. I think it can really take some time to reach the ultimate diagnosis for most of these conditions. Another challenging aspect, which I alluded to earlier, is sometimes when genetic testing might come back inconclusive or nonrevealing, and there remains some diagnostic uncertainty despite best efforts and a thorough workup -that can be frustrating as well, sometimes. Again, our knowledge of these genetics and the genetic mutations underlying these disorders is still really evolving. But on the flip side, there's a lot of rewarding aspects as well. I think one of the most rewarding aspects is trying to help patients identify interventions that improve their quality of life, and working with the patients and their families (who oftentimes become very expert in their own rare conditions in their own right), and working amongst the interdisciplinary teams. So many of these conditions are associated with extraneurologic manifestations, and so patients need coordination of care with other specialists. Hereditary spastic paraplegia is a great example, as well as Friedreich ataxia, where you often work closely with the cardiologist and of course, ALS, where there are a lot of multidisciplinary needs. Dr Nevel: Yeah, I'm so glad that you mentioned that because, in neurology in general (and specifically in this area), I can imagine the benefit to patients when there are multiple specialists involved in their care who are experts in the various aspects that are impacted from their underlying condition. Shifting gears a little bit - but going back to something that you've mentioned a few times, about making sure that we don't have a blind spot to genetic myelopathies, and that we consider this in part of our differential diagnosis when we're evaluating patients - in the patient who doesn't have an extensive family history of the exact same neurological symptoms, when should we consider genetic testing for patients that we're seeing in clinic? Like, at what point should we say, “Okay, we've done the other tests and now is the time to consider genetic testing.” Because I think, unless somebody has that really strong family history, it's probably not on the top of your list to do it right away, for a variety of reasons. Dr Stavros: I think you make a great point. Family history is tricky because, typically, we use that as a really strong clue of an inherited disorder of any type. But it can be tricky because, for a variety of reasons, it might be negative. Sometimes there is a de novo mutation, or there's variable phenotypes within the family, variable penetrance within the same family. Autosomal recessive inheritance can actually be, sometimes, hard to pick out. Or sometimes, patients don't have knowledge of their family members' medical histories. For all of these reasons, there may be information lacking in the family history. But I would say one of the most important things to exclude when you're working up patients initially is, of course, acquired causes of myelopathy, because you wouldn't want to miss a more treatable cause. And so, things like structural causes, nutritional, vascular or demyelinating causes (things that are explored more deeply in some of the other articles in this issue) are important. But if you've excluded acquired causes despite lacking a strong family history, I think, at that point, it's worth broadening your differential diagnosis to consider whether you might have reason to suspect a genetic myelopathy, particularly if you have some extraneurologic manifestations, some systemic symptoms that might be a clue towards a more systemic process. In genetic myelopathy, sometimes imaging can actually be quite helpful. It helps you exclude - MRI of the spine can help you exclude acquired causes, but it also helps you sometimes get clues toward a genetic cause. Typically, the finding might be either normal or show some spinal cord atrophy (but typically without signal change, so that can sometimes be a clue). Dr Nevel: What's one mistake that is made in managing patients with genetic myelopathies? Maybe “mistake” is too strong a word; maybe “misconception” about treating patients with genetic myelopathies. Dr Stavros: That's a great question. I think that one of the, maybe, misconceptions might be that these are homogeneous entities, these different diseases. But one of the things that surprised me anew in going back to research this topic and prepare this article was a reminder of just how variable both the genotypes and the phenotypes are within what we consider sometimes just one diagnosis, like hereditary spastic paraplegia, for example, spinocerebellar ataxia. There's so many different presentations and genotypes associated with these. It's really a family of different conditions. You could say the same thing about ALS as well. So, the spectrum of disease, I think, is important to recognize. Dr Nevel: Yeah, and I can imagine because of that spectrum of disease, just having an open mind in considering genetic testing and not excluding a potential genetic cause because it doesn't fit into what we think is the most typical presentation of that genetic condition. Dr Stavros: Yes - I'm in total agreement. Dr Nevel: I've asked you about what some of the misconceptions are and what some of the challenges are, but what's the most rewarding part about taking care of patients with genetic myelopathies for you? Dr Stavros: I think one of the most rewarding parts has to be working with the patients and the families. Like I mentioned earlier, sometimes they become so expert in their own conditions - it's amazing. And, working with them, working with the interdisciplinary teams, is a really rewarding process. I think that the more I've encountered patients with some of these rare conditions, the more I've learned from their stories and experiences, and so, that's, I think, been the most rewarding aspect to me. Dr Nevel: You've mentioned the multidisciplinary team a couple of times that we've talked about this, but who specifically do you usually include or contributes to the care of these patients? Dr Stavros: It may depend on the condition in question. So, for example, for Friedreich ataxia, there's always going to be a cardiologist involved in the patient's care. For ALS, there's going to be a larger team. For those who are familiar with ALS multidisciplinary clinics, this often includes physical therapy, speech therapy, nursing, pulmonary, and many others. And so, it really depends. I think in most cases though, genetics evaluation and genetic counseling is a really important piece. Dr Nevel: How do you work with the genetic counselors in counseling families about testing other family members? Because that's something that's really challenging in genetic conditions, especially for people with children that may be underage, and this is a really complicated topic. But how do you approach that? Dr Stavros: I think that it may depend on your particular institution. Where I'm at, typically, that's something that our genetics department will take the lead on and they will meet with the patient first and then also meet with and bring in any interested family members who are hoping to pursue the possibility of testing themselves. There's a bit of controversy or differing opinions around genetic testing, specifically for presymptomatic individuals for inherited ALS, because - certainly, there's pros and cons for being tested for any condition, but some special considerations come into play when someone is presymptomatic. There's actually been studies done, in particular, on patients who have a family history of ALS who are presymptomatic, and generally, the studies have shown that those patients are usually - the majority - in favor of being tested. But it does certainly bring up some ethical implications. Of course, any discussion is going to be undertaken with the goal of informing the patient and discussing the risks versus the benefits in detail. There's actually recommendations on the principles and the practice of presymptomatic testing for ALS, which is available and referenced in the article. Dr Nevel: Do you think as - hopefully, in the future, as more treatments become available - that presymptomatic genetic testing could play a role in how we manage patients? Dr Stavros: I think that's a great thought. I think it may, especially as more treatments become available, I think there may be a greater interest in demand for finding out early whether you might have a likelihood of developing a certain condition so that you can plan accordingly and perhaps even pursue treatments early on. Dr Nevel: You know, you mentioned this (and this isn't maybe quite exactly the same thing), but in SMA - you mentioned newborn screening for SMA and new treatment for SMA, and that newborn screening is not always a standard, and that there's controversy around that, now that we have treatment for it. Dr Stavros: Yes. That's another area where some controversy comes up as well, as far as cost and treatment, for sure. Dr Nevel: Thank you, Dr Stavros, for joining me on Continuum Audio. Again, today we've been interviewing Dr Kara Stavros, whose article on genetic myelopathies appears in the most recent issue of Continuum on spinal cord disorders. Be sure to check out Continuum Audio podcasts from this and other issues. And thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, please consider subscribing to the journal. There's a link in the episode notes. We'd also appreciate you following the podcast and rating or reviewing it. AAN members, go to the link in the episode notes and complete the evaluation to get CME for this episode. Thank you for listening to Continuum Audio.

*SOLIDARITY EPISODE* This month in partnership with Alport Syndrome Foundation! Our Carrier Connections program features a different X-linked condition each month with the goal to increase awareness of X-linked conditions and how they impact the lives of women and girls. Some of these X-linked conditions are part of a larger disease umbrella with other types of inheritance patterns. This month, we are featuring Alport syndrome. Alport syndrome is an inherited disorder caused by mutations, or changes, in the genes COL4A3, COL4A4, and COL4A5 that inhibit their ability to produce a protein called collagen IV. There are four main types of Alport syndrome characterized by their mode of inheritance; the X-linked version of this syndrome, X-linked Alport syndrome (XLAS), is the most commonly reported and brought on specifically by a defective COL4A5 gene. Other inheritance forms include autosomal recessive, autosomal dominant, and digenic. Alport syndrome is most frequently associated with symptoms of progressive kidney disease as well as bilateral sensorineural hearing loss and eye abnormalities. Today, we are bringing on December West. December has been married to Tarik West for 19 years. They have five children Alexis, Obed, Xyia, Nhalani, and Othniel. They reside in Akron, Ohio. Nhalani, who is 12-year-old now, was diagnosed with autosomal recessive Alport syndrome at the age of 6. Nhalani was misdiagnosed several times. Several years later, after a failed hearing screening and diagnosed with bilateral sensorineural hearing loss, Nhalani was referred to a geneticist who properly diagnosed her with autosomal recessive Alport syndrome. Carrier Connections is sponsored by Kyowa Kirin, Amgen, and Sanofi. For more information about our organization, check out ⁠⁠⁠⁠⁠⁠rememberthegirls.org⁠⁠⁠⁠⁠⁠.

Want to get a clearer picture of your whole family tree but lack information about your forebears because they weren't wealthy? Check out My Family Pattern's blog series to see how you can still find your ancestors! Visit https://myfamilypattern.com/poor-ancestors-are-not-invisible-part-1-pension-applications/ to learn more! My Family Pattern, LLC City: Austin Address: 1806 Scotty Trail Website https://www.myfamilypattern.com Phone +1 314 705 2568 Email myfamilypattern@gmail.com

Anne and Mike continue their conversation with David Rintell, Head of Patient Advocacy at BridgeBio, in part two of our autosomal dominant polycystic kidney disease (ADPKD) episode. Anne describes her recovery from the first kidney transplant along with the complications she attributes to her two native kidneys which were not removed during the initial surgery and issues with polycystic liver disease. In the 11 years following, Anne endured an operation to remove her native kidneys, followed by a double organ transplant, giving her both a new liver and kidney. Her first kidney transplant was generously gifted by a friend. However, Anne received her new liver and second kidney from a deceased donor, a distinctly different process. Anne and Mike express their gratitude for their good fortune while acknowledging the courage of the donor family to make the decision to give an extension on life to another human, when their loved one could no longer live.   Check out Anne and Mike's journey in their video, "The Search and the Gift" https://vimeo.com/33405248 . For more information about organ donation, visit http://donatelife.net/    To learn more about ADPKD, listen to Part 1 to hear Rachel Groth, Ph.D., Vice President of Research at BridgeBio X, explain why ADPKD develops, how it affects the kidneys, what complications may arise from ADPKD and why individuals with end-stage kidney disease receive dialysis or kidney transplants.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.04.547688v1?rss=1 Authors: Schultz, S., Liu, L., Schultz, A., Fitzpatrick, C., Levin, R., Bellier, J.-P., Shirzadi, Z., Mathurin, N., Chen, C., Benzinger, T., Day, G., Farlow, M., Gordon, B., Hassenstab, J., Jack, C., Jucker, M., Karch, C., Lee, J., Levin, J., Perrin, R., Schofield, P., Xiong, C., Johnson, K., McDade, E., Bateman, R., Sperling, R., Selkoe, D., Chhatwal, J., the Dominantly Inherited Alzheimer's Network Investigators Abstract: Background: The balance between production, clearance, and toxicity of A{beta} peptides is central to Alzheimer's disease (AD) pathobiology. Though highly variable in terms of age at symptom onset (AAO), hundreds of variants in PSEN1 cause autosomal dominant forms of AD (ADAD) with nearly complete penetrance. PSEN1 forms the catalytic core of the {gamma}-secretase complex and thereby directly mediates the production of longer, aggregation-prone A{beta} peptides relative to shorter, non-aggregating peptides. We hypothesized that the broad AAO and biomarker heterogeneity seen across ADAD would be predictable based on mutation-specific differences in the production of A{beta} species. Methods: A{beta}-37, 38, 40, 42, and 43 production was quantified from 162 unique PSEN1 variants expressed in HEK293 cells. Prediction of AAO was carried out in 107 variants with available AAO and then replicated in 55 variants represented across 190 PSEN1 mutation carriers who have detailed cognitive and biomarker data from the Dominantly Inherited Alzheimer's Network (DIAN). Results: Variations in A{beta} production across the 162 mutations examined in cell-based models were highly predictive of AAO. In those with corresponding in vivo data from the DIAN study, our cell-based {gamma}-secretase composite was strongly associated with biomarker and cognitive trajectories. Conclusions: These findings elucidate the critical link between {gamma}-secretase function, A{beta} production, and AD progression and offer mechanistic support for the amyloid hypothesis. The approach used here represents a powerful tool to account for heterogeneity in disease progression in ADAD clinical trials and to assess the pathogenicity of variants of unknown significance or with limited family history. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Title: “We named the new kidney - bean.” Anne is living with autosomal dominant polycystic kidney disease, (ADPKD)   Anne joins David Rintell, Head of Patient Advocacy at BridgeBio to talk about how autosomal dominant polycystic kidney disease (ADPKD) has impacted her and the lives of her family members. ADPKD weaves through the branches of Anne's family tree for generations. When Anne was only six years old, her father died at 46 of ADPKD related kidney failure, dialysis, and kidney transplantation. Two of Anne's five siblings have ADPKD. One had a successful kidney transplant, but another sibling died while on the waiting list for a new kidney. Anne wasn't surprised by her ADPKD diagnosis at age 25 and was hopeful for a better outcome than experienced by her father and her sibling since she received the diagnosis at a younger age. Progress was not reassuring to Mike, Anne's husband, when Anne's kidney function declined to less than 30%. Anne needed a kidney transplant, and soon. Motivated to find a donor and save her life, Mike created a robust campaign to locate a kidney for Anne. After many months of social posts, connections, conversations, prayers, and a documentary, a donor was discovered – a perfect match. The surgery was much quicker than the campaign. Anne left the hospital with her new kidney, appropriately named “bean,” just three days after her surgery. Rachel Groth, Ph.D., Vice President of Research at BridgeBio X, the company's dedicated lab space focused on cutting-edge early research discovery, provides an overview of ADPKD, a genetic condition that causes small fluid-filled sacs called cysts to develop in the kidneys. She explains why ADPKD develops, how it affects the kidneys, what complications may arise from ADPKD and why individuals with end-stage kidney disease receive dialysis or kidney transplants.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.22.546046v1?rss=1 Authors: He, K., Sun, X., Chen, C., Luc, S., Hao, J., Zhang, Y., Huang, Y., Wang, H., Ling, K., Hu, J. Abstract: Tubulin polyglutamylation is a post-translational modification that occurs primarily along the axoneme of cilia. Defective axoneme polyglutamylation impairs cilia function and has been correlated with ciliopathies, including Joubert Syndrome (JBTS). However, the precise mechanisms regulating proper axoneme polyglutamylation remain vague. Here, we show that Cyclin-Dependent Kinase 6 (CDK6), but not its paralog CDK4, localizes to cilia base and suppresses axoneme polyglutamylation by phosphorylating RAB11-interacting protein FIP5 at site S641, a critical regulator of cilia import of glutamylases. S641 phosphorylation disrupts the ciliary recruitment of FIP5 by impairing its association with RAB11, thereby reducing the ciliary import of glutamylases. Interestingly, significant upregulation of CDK6 and defective axoneme polyglutamylation were observed in Autosomal dominant polycystic kidney disease (ADPKD) cells. Encouragingly, the FDA-approved CDK4/6 inhibitor Abemaciclib can effectively restore cilia function in JBTS and ADPKD cells with defective glutamylation and suppresses renal cystogenesis in an ex vivo ADPKD model. In summary, our study elucidates regulatory mechanisms governing axoneme polyglutamylation and suggests developing CDK6-specific inhibitors could be a promising therapeutic strategy to enhance cilia function in ciliopathy patients. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In this week's podcast, Neurology Today's editor-in-chief discusses the FDA approval of an antipsychotic for agitation in dementia, elevated risk for Parkinson's in Camp Lejeune Marines exposed to contaminated water, a gene variant delays the onset of symptoms in man with autosomal dominant Alzheimer's. This podcast is sponsored by argenx. Visit www.vyvgarthcp.com for more information.

Rodney Cromwell "The Winter Palace" - https://www.happyrobots.co.uk/ Jamila & The Other Heroes "Ya Habibi, La!" - Bazaar Bizarre www.jamilaandtheotherheroes.com The Dirty Nil "Celebration" - Free Rein To Passions www.thedirtynil.com The Breathing Method "Indie Darkness" (featuring Crostpaths) www.thebreathingmethod.band Kathleen Turner Overdrive "Gurlzilla" - Autosomal https://www.facebook.com/musicalrelics ******************* ALBUM FOCUS: A reoccurring series focusing on new and outstanding concept, compilation and tribute albums. The Legends Of Tomorrow: The Weather at World's End: 1997–2022 Northern Island's Colin Harper curates a collection of songs from fellow studio collaborators and friends over a 25-year span "All We Need Is Love" (2022) "Better Weather" (2022) "My Heart Is Broken" (1997) "When You Needed" (1997) ********************** Lara Hope & The Ark-Tones "Here To Tell The Tale" - Here To Tell The Tale https://www.larahopeandtheark-tones.com/ Drew Young "Bourbon & Bad Decisions" www.drewyoungband.com Aistè "What's Going On" - Theory Of Everything https://www.aistemusic.com/ Ben Reel "Hardwired Blues" - Come a Long Way www.benreel.com Mister Rabbit "Stirring Absent Pots" - End Of History Illusion EP https://himisterrabbit.bandcamp.com/ Professor Louie & The Crowmatix "Work It Out" - Strike Up The Band www.professorlouie.com Malcolm Holcolmbe "The Wind Doesn't Know You" - Bits & Pieces www.malcolmholcombe.com ***************************** MÍO "Fra et annet sted" 'Ingen tid å miste https://www.miomusikk.com/ Max Forleo "The Black Curtain" - www.maxforleo.com The Rifters "At The Foot Of The Mountain" - The Enchanted World www.rifters.net William Prince "Tanqueray" - Stand In The Joy www.williamprincemusic.com Open Road "Dimming Of The Day" - Skylark www.openroadmusic.net Boa Morte "Mountain" - The Total Space www.boamorte.com ******************* Closing music: MFSB "My Mood" - Universal Love Running time: 4 hours, 21 minutes --- Send in a voice message: https://podcasters.spotify.com/pod/show/radiocblue/message Support this podcast: https://podcasters.spotify.com/pod/show/radiocblue/support

This podcast is incredibly HY. You will see a lot of this stuff on your exams. Enough said! Audio Download

The CardioNerds Cardiovascular Genomics Series continues! In this episode Dr. Dan Ambinder (CardioNerds Cofounder and Interventional Cardiologist), Dr. Anjali Wagle (FIT Ambassador at Johns Hopkins) and Dr. James Sampognaro (medicine resident at Johns Hopkins Osler Medicine Residency) learn from Dr. Allison Hays (Associate Professor of Medicine, Division of Cardiology, Johns Hopkins CMR researcher and Medical Director of Echocardiography) and Dr. Cindy James (Associate Professor of Medicine and certified genetic counselor at Johns Hopkins with research focusing on cardiovascular genetic counseling and arrhythmogenic cardiomyopathies). They discuss arrhythmogenic RV cardiomyopathy as the context to learn about genetic counseling and family screening.  Episode script and notes were developed by Dr. Anjali Wagle. Audio editing by CardioNerds Academy Intern, student doctor Chelsea Amo Tweneboah. This episode was developed in collaboration with the American Society of Preventive Cardiology and is supported with unrestricted educational funds from Illumina, Inc. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds. This CardioNerds Cardiovascular Genomics series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs. Check out this REVIEW describing the “Multimodality Imaging in Arrhythmogenic Right Ventricular Cardiomyopathy” by Nitin Malik, Allison Hays, and colleagues.   For related episodes, please enjoy these case-based discussions:  Ep 56. Case Report: Arrhythmogenic Desmoplakin Cardiomyopathy – Northwestern University  Ep 74. Case Report: Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) – Summa Health  Pearls • Notes • References CardioNerds Cardiovascular Genomics PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Show notes - Genetic Counseling & Family Screening in Arrhythmogenic Cardiomyopathies Notes (developed by Dr. Anjali Wagle)   What is the underlying pathophysiology of arrhythmogenic RV cardiomyopathy (ARVC)?  Fibrofatty replacement cardiac myocytes  Associated with genetically mediated disruption of desmosomal proteins   This leads to thinning and weakness of the heart that can lead to aneurysms and progressive dilatation and failure of the right ventricle (RV)  How is ARVC diagnosed?  2010 taskforce criteria (Marcus et al, 2010):    RV structural abnormalities including findings seen on echocardiogram, MRI, and RV angiography  Pathological criteria  Repolarization abnormalities   Depolarization/conduction abnormalities   Ventricular arrhythmias   Genetics and/or family history   How does ARVC present?   Young, healthy individual will have symptoms of arrhythmias (syncope, pre-syncope, SCD) or heart failure  Family screening   What are the inheritance and genetic factors of ARVC?  Autosomal dominant pattern  Low penetrance and variable expressivity   Half of patients who are index cases will be found to have a mutation in the desmosomal gene.   What are the most common mutations associated with ARVC?  Most commonly the genes involved are plakophilin-2 (PKP-2) and desmoplakin.   For PKP-2 the most common mutations are truncating mutations.   In patients who have inherited two truncating mutations, this will result in neonatal lethality.   Is there a difference in the genetic factors of left and right arrhythmogenic cardiomyopathy?   ACM is disproportionally a right dominated cardiomyopathy. Left dominated cardiomyopathy has a different genetic profile.   Pathogenic variants in desmoplakin disproportionally cause biventricular forms of ACM or left dominated forms.  

This video discusses long QT syndrome as an example to discuss medical conditions that are inherited in an autosomal dominant fashion. This is the first video in a 3-video series on Genetic Diseases. It was created by Dr. Rozlyn Boutin, a resident at British Columbia's Children's Hospital in Vancouver, BC, Canada in collaboration with Dr. Caitlin Chang, a medical geneticist at BC Children's.

This video discusses long QT syndrome as an example to discuss medical conditions that are inherited in an autosomal dominant fashion. This is the first video in a 3-video series on Genetic Diseases. It was created by Dr. Rozlyn Boutin, a resident at British Columbia's Children's Hospital in Vancouver, BC, Canada in collaboration with Dr. Caitlin Chang, a medical geneticist at BC Children's.

At birth, Jessica's physician noticed she had low levels of calcium. Genetic testing later confirmed that she had autosomal dominant hypocalcemia type 1 (ADH1) with a calcium receptor (CaSR) gene mutation. Jessica had complications due to ADH1 quite early in life. Before Jessica started kindergarten, she had painfully passed her first kidney stone. Fiercely protective and attentive, Jessica's mother quit her job to take care of Jessica full-time. She researched and provided Jessica with the latest cutting-edge treatments.  Despite the challenges of living with ADH1, Jessica has done well. She is a hopeful, new mother who is ready to do whatever it takes to take care of her child. She has a graduate degree and works to provide mental health care for her clients. Mary Scott Roberts, M.D., senior director of clinical development at BridgeBio Cardiorenal, joins to provide an overview of ADH1. She describes how low or elevated levels of calcium can cause muscle cramps, brain fog, fatigue, seizures, and other symptoms in individuals living with ADH1.

Today's episode of Research Like a Pro is about autosomal DNA coverage. We define the term, discuss why it's important, and share examples and formulas. Learn how you can find more relevant DNA matches when you include additional test takers who descend through unique child lines.  Links Find More Ancestors with Autosomal DNA by Increasing Coverage - https://familylocket.com/find-more-ancestors-with-autosomal-dna-by-increasing-coverage/ RLP 204: Recruiting Test Takers for an Autosomal DNA Project - https://familylocket.com/rlp-204-recruiting-test-takers-for-an-autosomal-dna-project/ Research Like a Pro Resources Research Like a Pro: A Genealogist's Guide book by Diana Elder with Nicole Dyer on Amazon.com - https://amzn.to/2x0ku3d Research Like a Pro eCourse - independent study course -  https://familylocket.com/product/research-like-a-pro-e-course/ RLP Study Group - upcoming group and email notification list - https://familylocket.com/services/research-like-a-pro-study-group/ Research Like a Pro with DNA Resources Research Like a Pro with DNA: A Genealogist's Guide to Finding and Confirming Ancestors with DNA Evidence book by Diana Elder, Nicole Dyer, and Robin Wirthlin - https://amzn.to/3gn0hKx Research Like a Pro with DNA eCourse - independent study course -  https://familylocket.com/product/research-like-a-pro-with-dna-ecourse/ RLP with DNA Study Group - upcoming group and email notification list - https://familylocket.com/services/research-like-a-pro-with-dna-study-group/ Thank you Thanks for listening! We hope that you will share your thoughts about our podcast and help us out by doing the following: Share an honest review on iTunes or Stitcher. You can easily write a review with Stitcher, without creating an account. Just scroll to the bottom of the page and click "write a review." You simply provide a nickname and an email address that will not be published. We value your feedback and your ratings really help this podcast reach others. If you leave a review, we will read it on the podcast and answer any questions that you bring up in your review. Thank you! Leave a comment in the comment or question in the comment section below. Share the episode on Twitter, Facebook, or Pinterest. Subscribe on iTunes, Stitcher, Google Play, or your favorite podcast app. Sign up for our newsletter to receive notifications of new episodes - https://familylocket.com/sign-up/ Check out this list of genealogy podcasts from Feedspot: Top 20 Genealogy Podcasts - https://blog.feedspot.com/genealogy_podcasts/

$5 Q-BANK: https://www.patreon.com/highyieldfamilymedicine Intro 0:30, Potter sequence 1:40, Renal agenesis 2:40, Renal cysts 4:01, Autosomal dominant polycystic kidney disease (ADPKD) 4:59, Autosomal recessive polycystic kidney disease (ARPKD) 6:40, MCKD and JNPH 7:58, Tuberous sclerosis 8:19, Von Hippel Lindau 8:57, Horseshoe kidney 9:53, Ureteropelvic junction obstructions 10:34,  Voiding cystourethrography (VCUG) 11:10, Vesicoureteral reflux 12:00, Posterior urethral valves 11:21, Hypospadias 14:15, Epispadias and bladder-exstrophy-epispadias-complex (BEEC) 15:10, Prune Belly Syndrome 15:58, Disorders of sexual development 16:36, Ambiguous genitalia 17:39, Embryology of sex differentiation 20:11, Anti-Mullerian hormone 20:52, Testosterone 21:19, Dihydrotestosterone 21:50, 5a-reductase deficiency 22:04, Androgen insensitivity syndrome 22:21, Aromatase deficiency 23:29, Congenital adrenal hyperplasia 24:25, 21-Hydroxylase deficiency 26:35, Other causes of CAH 30:36, Kallman syndrome 32:12, Semil-Lemil-Opitz syndrome 32:53, Practice questions 33:22

Today's episode of Research Like a Pro is about setting up a web page to share with potential DNA test takers. Nicole talks about the Daniel Arnold project to find Daniel's parents. Daniel was born 6 August 1806 and married Lydia Willey. We discuss autosomal DNA coverage, making living people in reports anonymous, and targeted testing of people from independent child lines. We also review the current research and clues pointing to Daniel's parents. Links Covering Your Bases: Introduction to Autosomal DNA Coverage - by Paul Woodbury at https://www.legacytree.com/blog/introduction-autosomal-dna-coverage Daniel Arnold Research Project to recruit test takers - https://familylocket.com/parents-of-daniel-arnold/  Research Like a Pro Resources Research Like a Pro: A Genealogist's Guide book by Diana Elder with Nicole Dyer on Amazon.com - https://amzn.to/2x0ku3d Research Like a Pro eCourse - independent study course -  https://familylocket.com/product/research-like-a-pro-e-course/ RLP Study Group - upcoming group and email notification list - https://familylocket.com/services/research-like-a-pro-study-group/ Research Like a Pro with DNA Resources Research Like a Pro with DNA: A Genealogist's Guide to Finding and Confirming Ancestors with DNA Evidence book by Diana Elder, Nicole Dyer, and Robin Wirthlin - https://amzn.to/3gn0hKx Research Like a Pro with DNA eCourse - independent study course -  https://familylocket.com/product/research-like-a-pro-with-dna-ecourse/ RLP with DNA Study Group - upcoming group and email notification list - https://familylocket.com/services/research-like-a-pro-with-dna-study-group/ Thank you Thanks for listening! We hope that you will share your thoughts about our podcast and help us out by doing the following: Share an honest review on iTunes or Stitcher. You can easily write a review with Stitcher, without creating an account. Just scroll to the bottom of the page and click "write a review." You simply provide a nickname and an email address that will not be published. We value your feedback and your ratings really help this podcast reach others. If you leave a review, we will read it on the podcast and answer any questions that you bring up in your review. Thank you! Leave a comment in the comment or question in the comment section below. Share the episode on Twitter, Facebook, or Pinterest. Subscribe on iTunes, Stitcher, Google Play, or your favorite podcast app. Sign up for our newsletter to receive notifications of new episodes - https://familylocket.com/sign-up/ Check out this list of genealogy podcasts from Feedspot: Top 20 Genealogy Podcasts - https://blog.feedspot.com/genealogy_podcasts/

The Journal RETINA is devoted exclusively to diseases of the retina and vitreous. These podcasts are intended to bring to its listeners summaries of selected articles published in the current issue of this internationally acclaimed journal.  

Polycystic kidney disease is an inherited disorder where clusters of cysts develop within the kidneys, causing the kidneys to enlarge and lose function over time. The cysts, which are noncancerous sacs containing fluid, vary in size, and they can grow to be large. This disorder can occur in children and adults.The two main types of polycystic kidney disease, caused by different genetic flaws, are: Autosomal dominant polycystic kidney disease (ADPKD). Signs and symptoms of ADPKD often develop between the ages of 30 and 40. In the past, this type was called adult polycystic kidney disease, but children can develop the disorder.Only one parent needs to have the disease for it to pass to the children. If one parent has ADPKD, each child has a 50% chance of getting the disease. This form accounts for most of the cases of polycystic kidney disease.  Autosomal recessive polycystic kidney disease (ARPKD). This type is far less common than is ADPKD. The signs and symptoms often appear shortly after birth. Sometimes, symptoms don't appear until later in childhood or during adolescence.Both parents must have abnormal genes to pass on this form of the disease. If both parents carry a gene for this disorder, each child has a 25% chance of getting the disease. Polycystic kidney disease also can cause cysts to develop in the liver and elsewhere in the body. The disease can cause serious complications, including high blood pressure and kidney failure.The disease varies greatly in its severity, and some complications from polycystic kidney disease are preventable. Lifestyle changes and treatments might help reduce damage to the kidneys from complications, but long-term interventions, including dialysis or kidney transplant, are sometimes needed.On this special Ask the Mayo Mom edition of the Mayo Clinic Q&A podcast, host Dr. Angela Mattke is joined by Dr. Christian Hanna, a pediatric nephrologist with Mayo Clinic Children's Center to discuss PKD in children.

Brianna was diagnosed with Osteopetrosis at the age of 2. Osteopetrosis, which literally means “stone bone“, is a disorder that causes an individual's bones to be so weak and frail that simply bumping into an object will cause their bones to break.Autosomal recessive osteopetrosis (ARO), the type of osteopetrosis with which Brianna was born, is one of two forms of the disorder and is the most severe. ARO makes itself apparent during infancy and usually presents with abnormally dense skull bones that pinch nerves in the head and face resulting in vision loss and possibly the loss of other senses. This is the cause of Brianna's blindness.While Brianna has been living with this disorder her entire life, God continues to give her the strength to endure the challenges with which she is confronted. Brianna has broken nearly every bone in her body, and still leads a full life. Her surgical scars tell stories of every battle she has faced and overcome. Brianna founded Scarred Not Broken to serve as a platform to remind other individuals with disabilities that, even if the battles of this world leave them scarred, they are certainly not broken! Check out Brianna's organization at www.scarrednotbroken.org

This is an article summary of "Asymptomatic Pyuria as a Prognostic Biomarker in Autosomal Dominant Polycystic Kidney Disease" by Fouad Chebib on behalf of coauthors.

Filippa är mamma till 7 barn, varav två av dem bor i himmelen. Meya och Wilya dog båda två år 2015, med nästan exakt 9 månaders mellanrum. Meya föddes i slutet på vecka 36. Det var en alldeles underbar förlossning fram tills dess att personalen springer iväg med den lilla bebisen till återupplivningsbordet. Ungefär 10 minuter efter sin födsel stannar Meyas hjärta och personalen jobbar i en timme med hennes kropp innan hon dödförklaras. Man misstänkte ett kronosomfel, som inte såg ut att vara genetiskt. Några månader senare när lillasyster låg i magen och via ett ultraljud i vecka 22, såg man att njurarna såg onaturliga ut till växten. Kontroller visade att föräldrarna trots allt bar på ett genfel och båda flickornas avvikelser, autosomal resesiv polycystisk njursjukdom, som konstaterades att inte vara förenligt med ett liv, berodde på detta. Föräldrarna fick då ansöka om att få godkänt att avbryta graviditeten och Filippa fick föda ut Wilya, en död liten miniatyrmänniska som var alldeles perfekt .

Occurring on or transmitted by a chromosome other than one of the sex chromosomes.

Welcome back to the Ancestral Findings Podcast . . . Autosomal DNA is a different type of DNA research you might want to consider. In fact, it is the most common and popular type of DNA testing done for genealogical purposes today. This is what autosomal DNA is, what it can tell you, and the ways you can use it to more accurately add to your family tree... Podcast Show Notes: https://ancestralfindings.com/autosomal-dna-a-closer-look-at-dna-research-3/  Genealogy Clips Podcast: https://genealogyclips.com Historical Postcard Giveaway: https://ancestralfindings.com/postcard-giveaway/ Free Genealogy eBooks: https://ancestralstuff.com Hard To Find Surnames: https://ancestralfindings.com/surnames Follow on Facebook: https://www.facebook.com/AncestralFindings Support Ancestral Findings: https://ancestralfindings.com/donation #Genealogy #AncestralFindings #GenealogyClips

Visit the show notes page at Genealogy Gems. This episode is brought to you by our wonderful sponsors: StoryworthGive your relatives a meaningful gift with StoryWorth. Get started right away with no shipping required by going to   You'll get $10 off your first purchase!  From Lisa: “I use MyHeritage for my own genealogy research. It makes all the difference!” Episode Topic: DNA Problem Solving  Maybe it's as simple as having a ton of matches and not knowing what to do with them. How do you keep track of all those matches. How to you know which matches to focus on? How can you can use all your matches to do what you really want to do, which is learn more about my family history? In this episode Sara Allen of the Genealogy Center at the Allen County Public Library joins me to share strategies for working past many of these problems. I wanted to talk to Sara because she's not a biologist, or a Genetic Genealogy Guru. She's like you and me: she's passionate about family history! She shares genetic genealogy with folks in a very practical, and easy-to-understand way. Video and Show NotesThis audio comes from my YouTube video series Elevenses with Lisa . Genealogy Gems Premium Members have exclusive access to the downloadable show notes "cheat sheet" handout. Premium Members also have access to all of the archived earlier episodes. To access the Elevenses with Lisa Premium Member , log in to your membership at  and under in the main menu under Premium go to Premium Videos and click on Elevenses with Lisa. Become a Genealogy Gems Premium MemberPremium Members have exclusive access to: Video classes and downloadable handouts The Genealogy Gems Premium Podcast Elevenses with Lisa downloadable show notes PDF Become a Premium Member . Stay Up to Date with the Genealogy Gems NewsletterThe Genealogy Gems email newsletter is the best way to stay informed about what's available with your Premium eLearning Membership.  to sign up today. Follow Lisa and Genealogy Gems on Social Media: #genealogy #DNA

In this episode of Look Beneath the Surface: An Expert Dive into Alport Syndrome, Dr George Bakris welcomes Dr Jochen Reiser for a close look at what COL4A genotyping can tell us about the course and impact of Alport syndrome for both patients and their families. Additional resources are available through the Alport Syndrome Foundation at alportsyndrome.org.

In the debut episode of Look Beneath the Surface: An Expert Dive into Alport Syndrome, Dr George Bakris is joined by Dr Joshua Zaritsky to discuss the link between inherited genetic defects and the inflammation and fibrosis that drive disease progression in Alport syndrome.

Our family lineages can be powerful sources of support and healing if we uncover how to skillfully work with them. Even if you've never thought of your ancestors much before or if you feel they were duds (or worse!) discussed in this compelling episode are the myriad of psychological & spiritual benefits of doing so. Whether we know our family lineages or not, our ancestors are connected to us by energetic threads, and science has unequivocally proven their stories live in the marrow of our bones in the form of our DNA. Unpacked are safe & interesting ways you can create more revelation, guidance and connection in your life through accessing your family bloodlines. Plus when we learn to energetically and psychologically untangle ourselves from the baggage handed down osmotically to us from our families then we can focus on what is truly ours this lifetime to work on and create a genuinely original life.  SHOW NOTES: A Chinese proverb says to forget one's ancestors is to be a brooke without a source, a tree without a root. For some of us the idea of our ancestors is romantic & for others, our ancestors bring up complicated feelings intertwined with our family's very unique set of idiosyncratic tendencies, foibles and traumas.  Some of our ancestors' stories and lives may be interwoven into the fabric of colonialism, ecological degradation, racism, classism, sexisim, homophobia, oppression in various forms and other uncomfortable narratives. Yet the reality is we are all branches of a certain tree whose roots burrough so deeply down into the earth, you have ancestors who for certain who were also healers, teachers, songstresses, herbalists, artists, creators, seekers, inventors & visionaries.  So whether you are aware and enamored of your more recent ancestors or this thought about your “deep ancestors” (the one's whose names & stories you are unaware) ignites a spark in you to illuminate the fact that you are a direct descendent of brilliant earth wise geniuses who knew how to pay attention to the sky & its patterning, to be with the water and its nourishment, to work with fire and its alchemical ways, to work with the gusts & messages of the winds and to live in collaboration with the earth. They had to have in order to survive and preserve the genealogical line that you stand upon. These Beings most of whom slipped through history's fingers before everything was being recorded like today, delighted in the miracle of life, were humbled by the pulsing necessity of death, knew the beauty of wisdom and aging, honored the preciousness of their tribe and heard the hallowed call of spirit in their mundane tasks which opened up pathways of reverence within their minds and magic in their lives. When we take time to follow our branches through the trunk of our families to our roots, those roots then plug us into the ground of Being and bring us back into connection. Our lives in this  modern age full of hyper speed and detachment from the natural world has led to such a profound craving for so many, to such a deep soul depravity that many folks have turned to distracted activities and/or addictions which disconnect us even further from our own humanity and take us further away from our own souls. For those of us longing to find connection, revelations, healing guidance and even magic, connecting to our known or unknown ancestors is a powerful way to do this. Our lineages of family are connected to us by energetic threads and when we heal the baggage that either lives in our DNA, we release the baggage that was passed down to us and free the beings in our family who live on after us.  Offered are a variety of practical and accessible ways you can begin or to continue your relationship with your ancestors. Discussed is the anthropological concept of “Ancestor Worship.” Discussed is the psychological concept “Johari's Window.” Ancestry.com Africanancestry.com Discussed are Autosomal, Mitochondrial & Y-DNA tests. Our bodies in some sense are ancestral shrines. If we don't get to the root of our ancestral stories we can play them out. The ancestors were very much aligned with the wisdom of the earth and so can give us clues as to how to align with living in this way.  Connecting to an Ancestor Meditation is offered. (*Can be played over & over again) May we be their servants and carry their love & their hard won lessons into our lives and into this world.  ✨HUGE ANNOUNCEMENT!: The doors for the Modern Mystic Membership are now open! Monthly Mystic Members get access to a library of well over 100 yoga, meditation & breathwork classes as well as short “Mystic Hack” videos which have a myriad of topics ranging from: how to ground, protect and grow your energy; to astrology & tarot card videos; to developing one's psychic abilities and more! Get a sample of some FREE videos and find the Membership area here: modernmystic.love ✨Give it a 5 star, 1 line review on iTunes (takes literally 2 min either from an iPhone or via the iTunes store on all other devices). This is HUGE as it helps get it heard more which helps the podcast get supported. ✨Join conscious conversation & community in the Modern Mystic Podcast ✨ Private F-book Group: https://www.facebook.com/groups/959629444823656/ ✨Get inspiring insights on IG: @modernmysticlove

Many of us see children with joint pain, some of whom are incredibly bendy. But have they "got hypermobility" or even EDS? Join Dr Alice Leahy and Marisa McMillan in their wide ranging discussion about EDS, hypermobility syndrome, arthritis, factors affecting how people perceive pain, and possible reasons why EDS has become more prominent on social media recently. ------------------------------------------------------------------------------------------------------------------------------------- Pearls include: The Beighton Score: not very useful in the local paediatric population and is not validated. ---- Ehlers Danlos Syndrome (EDS) is a collection of collagen disorders 13 subtyes of EDS, 12 of which have known genetic mutations and histopathological changes, the 13th - neither genetic nor histopathological changes, otherwise known as hypermobility EDS. ----The 3 types worth remembering are: ☆Vascular type EDS - very rare - usually present to genetics depts rather than to rheumatology department - FH vascular rupture, Distinctive facial characteristics. ☆☆Classical type EDS. Also rare. Extremely hypermobile. Excessively stretchy skin. Can pull skin out from forearm 6cm (upper range of normal 2cm) Autosomal dominant. Often very bruised with plentiful scarring on body. ☆☆☆Hypermobility type EDS: Beighton score of >6 pre-pubescent children; >4 in pubescent children ------ Joint pain is not a good indicator of inflammatory arthritis. ♡♡♡JIA usually presents with very little pain. Arthritis will present with joint swelling. If arthritis is suspected, request an ultrasound. A normal USS will exclude inflammatory disease. Blood tests are not helpful in diagnosing arthritis - neither are X-rays. ------------------------------------------------------------------------------------------------------------------------------------------------------------- Useful Resources: •••The 2017 international classification of the Ehlers–Danlos syndromes (Malfait et al) https://doi.org/10.1002/ajmg.c.31552 ••••The RCPCH position statement on establishing a correct diagnosis of Ehlers Danlos Syndrome hypermobility type (hEDS) in children and adolescents  https://www.rcpch.ac.uk/resources/establishing-correct-diagnosis-ehlers-danlos-syndrome-hypermobility-type-heds-children#footnote5_xb0pjtb •••Head First by Alistair Santhouse Head First: A Psychiatrist's Stories of Mind and Body https://www.amazon.co.uk/dp/1838950311/ref=cm_sw_r_apan_glt_fabc_6KB3WZ7BY8XBW3WEYA8Q •••It's All in Your Head by Suzanne O'Sullivan It's All in Your Head: Stories from the Frontline of Psychosomatic Illness https://www.amazon.co.uk/dp/0099597853/ref=cm_sw_r_apan_glt_fabc_M77GAQV12ES834PWHCTT

Aneuploidies are chromosome number abnormalities. Trisomies fall under the umbrella of aneuploidies. The term trisomy comes from tri, meaning tripled, and soma, meaning body—the tripling of a single chromosomal body. This serious genetic abnormality can have significant effects on development. There are two types of trisomies: X/Y and autosomal. The X/Y trisomies result from an extra copy of one of the sex chromosomes. They include conditions like Klinefelter syndrome (47, XXY) and triple X syndrome (47, XXX). Autosomal trisomies result from an extra copy of one of the 22 autosomal (nonsex) chromosomes and include several conditions we will discuss in more detail below. Trisomies can result from abnormal chromosome separation during meiosis or from an inherited joined chromosome. The most common type of joined chromosome is called a Robertsonian translocation and can lead to trisomies in offspring. Most trisomies are embryonic lethal abnormalities. Only trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome) are survivable until birth, and generally only trisomy 21 individuals survive infancy. After listening to this Audio Brick, you should be able to: Explain how a carrier of a Robertsonian translocation is at higher risk of having a child with a trisomy. Contrast the genetic etiology and clinical presentation of Down syndrome, Edwards syndrome, and Patau syndrome. Differentiate Down syndrome, Edwards syndrome, and Patau syndrome based on ultrasonographic findings and altered serum marker levels. You can also check out the original brick from our Cellular and Molecular Biology collection, which is available for free. Learn more about Rx Bricks by signing up for a free USMLE-Rx account: www.usmle-rx.com You will get 5 days of full access to our Rx360+ program, including nearly 800 Rx Bricks.  After the 5-day period, you will still be able to access over 150 free bricks, including the entire collections for General Microbiology and Cellular and Molecular Biology. *** If you enjoyed this episode, we'd love for you to leave a review on Apple Podcasts.  It helps with our visibility, and the more med students (or future med students) listen to the podcast, the more we can provide to the future physicians of the world. Follow USMLE-Rx at: Facebook: www.facebook.com/usmlerx Blog: www.firstaidteam.com Twitter: https://twitter.com/firstaidteam Instagram: https://www.instagram.com/firstaidteam/ YouTube: www.youtube.com/USMLERX Learn how you can access over 150 of our bricks for FREE: https://usmlerx.wpengine.com/free-bricks/ from our Musculoskeletal, Skin, and Connective Tissue collection, which is available for free. Learn more about Rx Bricks by signing up for a free USMLE-Rx account: www.usmle-rx.com You will get 5 days of full access to our Rx360+ program, including nearly 800 Rx Bricks.  After the 5-day period, you will still be able to access over 150 free bricks, including the entire collections for General Microbiology and Cellular and Molecular Biology.

The most common congenital cause of CKD, ADPKD is an important diagnosis to be aware of in adults. Come learn about its many complications and emerging therapies for the treatment of ADPKD. 

A client has Marfan syndrome—what does it mean for him? And what does it mean for massage? Listen in as we review what autosomal dominant means, and we enjoy some new vocabulary: dolichostenomelia (abnormally long, thin limbs) and arachnodactyly (spider-digits). We also learn about the potentially life-threatening complications of this genetic disorder.   Sponsors:       Anatomy Trains: www.anatomytrains.com     Books of Discovery: https://booksofdiscovery.com      Author Bio:       Ruth Werner is a former massage therapist, a writer, and an NCBTMB-approved continuing education provider. She wrote A Massage Therapist’s Guide to Pathology, now in its seventh edition, which is used in massage schools worldwide. Werner is also a long-time Massage & Bodywork columnist, most notably of the Pathology Perspectives column. Werner is also ABMP’s partner on Pocket Pathology, a web-based app and quick reference program that puts key information for nearly 200 common pathologies at your fingertips. Werner’s books are available at www.booksofdiscovery.com. And more information about her is available at www.ruthwerner.com.         Recent Article by Ruth:      “Spinal Fusion Surgery: Common, Complicated, Controversial,” Massage & Bodywork magazine, March/April 2021, page 34,      ABMP Pocket Pathology:      www.abmp.com/abmp-pocket-pathology-app      Resources:   Inna, Prashanth. “Marfan Syndrome (MFS).  (2020). June 18, 2020.    John Hopkins Medicine. “Marfan Syndrome.” Accessed April 7, 2021.    Loeys, B. L. et al. “Differential Diagnosis of Marfan Syndrome.” Adapted from “The Revised Ghent Nosology for the Marfan Syndrome.” Journal of Medical Genetics 47 (2010): 476. Accessed April 7, 2021.   The Marfan Foundation. “What is Marfan Syndrome?” Accessed April 6, 2021.    Autosomal dominant inheritance (image)   About our Sponsor: Anatomy Trains Anatomy Trains is a global leader in online anatomy education and also provides in-classroom certification programs for structural integration in the US, Canada, Australia, Europe, Japan, and China, as well as fresh-tissue cadaver dissection labs and weekend courses. The work of Anatomy Trains originated with founder Tom Myers, who mapped the human body into 13 myofascial meridians in his original book, currently in its fourth edition and translated into 12 languages. The principles of Anatomy Trains are used by osteopaths, physical therapists, bodyworkers, massage therapists, personal trainers, yoga, Pilates, Gyrotonics, and other body-minded manual therapists and movement professionals. Anatomy Trains inspires these practitioners to work with holistic anatomy in treating system-wide patterns to provide improved client outcomes in terms of structure and function.        Website: anatomytrains.com        Email: info@anatomytrains.com         Facebook: facebook.com/AnatomyTrains       Instagram: instagram.com/anatomytrainsofficial       YouTube: www.youtube.com/channel/UC2g6TOEFrX4b-CigknssKHA       

Today we'll be covering Lysosomal Storage Disorders, going along with this month's theme, Metabolic Disorders. If you haven't listened to our podcast before, each week we have a case-based discussion about a medical topic to help you study for the pediatric medicine board exam. Episodes are released every weekend, and the case is then reviewed and reinforced on social media throughout the week.   Follow the podcast on social media: Facebook- @portablepeds (www.facebook.com/portablepeds) Twitter- @portablepeds (www.twitter.com/portablepeds)   We'd love to hear from you via email at portablepeds@gmail.com!   Also, feel free to visit our website, www.portablepeds.com, for more content.   Today's Case:   A worried mother presents to your outpatient pediatric office with her 2 and a half year old son after scrapbooking during her free time in the pandemic. She states that he has overall been healthy without concern and because of the pandemic, they have not been in to see you for over a year. She became concerned a few days ago when she noticed that compared to previous pictures, her son's nose, tongue, lips, cheeks, and head have become bigger and he seems more “stiff” than before. On your exam, you note an inguinal hernia on the right, hepatomegaly, stiff joints, coarse facial features, and an unremarkable ophthalmologic exam. CBC in your lab is unremarkable. Which disease and appropriately paired genetic inheritance pattern are you most suspicious of?     Hurler syndrome, X-linked recessive inheritance   Hunter syndrome, X-linked recessive inheritance   Tay-Sachs disease, Autosomal recessive inheritance   Gaucher disease, Autosomal recessive inheritance   Niemann-Pick Disease, X-linked recessive inheritance   We would like to give an enormous thank you to Zack Goldmann for designing this podcast's logo and accompanying artwork. You can find more of his work at www.zackgoldmann.com.   The intro and outro of this podcast is a public domain song obtained from scottholmesmusic.com.   Intro/Outro- Hotshot by Scott Holmes   Disclaimer: This podcast is intended for healthcare professionals. The information presented is for general educational purposes only and should NOT be used as professional medical advice or for the diagnosis or treatment of medical conditions.   The views and opinions expressed do not represent the views and opinions of our employer or any affiliated institution. Expressed opinions are based on specific facts, under certain conditions, and subject to certain assumptions and should not be used or relied upon for any other purpose, including, but not limited to, the diagnosis or treatment of medical conditions or in any legal proceeding. Full terms and conditions can be found at portablepeds.com.   Thanks for listening! As always, please Rate and Review this podcast on Apple Podcasts, Facebook, or your favorite podcasting platform. Also, Subscribe to get all the latest episodes, and Share this episode with someone you think would enjoy it! Hope to see you real soon!  

Rare diseases affect nearly 30 million Americans each year. One rare, progressive kidney disease, known as Autosomal Dominant Polycystic Kidney Disease (ADPKD), is the most common, rare, inherited kidney disorder you’ve likely never heard of. My guest is Nephrologist, Dr. Meyon Park, Director of UCSF Polycystic Kidney Disease Center of Excellence, she shares the signs, symptoms and impact that ADPKD has on the kidneys.

Rare diseases affect nearly 30 million Americans each year. One rare, progressive kidney disease, known as Autosomal Dominant Polycystic Kidney Disease (ADPKD), is the most common, rare, inherited kidney disorder you’ve likely never heard of. My guest is Nephrologist, Dr. Meyon Park, Director of UCSF Polycystic Kidney Disease Center of Excellence, she shares the signs, symptoms and impact that ADPKD has on the kidneys.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.17.384669v1?rss=1 Authors: Arango-Gonzalez, B., Sen, M., Guarascio, R., Ziaka, K., del Amo, E. M., Hau, K., Poultney, H., Asfahani, R., Urtti, A., Chou, T.-F., Bolz, S., Deshaies, R. J., Haq, W., Cheetham, M. E., Ueffing, M. Abstract: Due to continuously high production rates of rhodopsin (RHO) and high metabolic activity, photoreceptor neurons are especially vulnerable to defects in proteostasis. A proline to histidine substitution at position 23 (P23H) leads to production of structurally misfolded RHO, causing the most common form of autosomal dominant Retinitis Pigmentosa (adRP) in North America. The AAA-ATPase valosin-containing protein (VCP) extracts misfolded proteins from the ER membrane for cytosolic degradation. Here, we provide the first evidence that inhibition of VCP activity rescues degenerating P23H rod cells and improves their functional properties in P23H transgenic rat and P23H knock-in mouse retinae, both in vitro and in vivo. This improvement correlates with the restoration of the physiological RHO localization to rod outer segments (OS) and properly-assembled OS disks. As a single intravitreal injection suffices to deliver a long-lasting benefit in vivo, we suggest VCP inhibition as a potential therapeutic strategy for adRP patients carrying mutations in the RHO gene. Copy rights belong to original authors. Visit the link for more info

A quick overview of autosomal dominant inheritance

Quickfire quiz on Autosomal Recessive and Dominant Inheritance!

Discussion of the mode of inheritance and notable example of autosomal recessive conditions

A quick quiz on Autosomal Recessive Conditions

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.27.222323v1?rss=1 Authors: Choi, B. Y., Lee, C. J., Oh, D.-Y., Jang, M. W., Lee, E. Abstract: Genes that are primarily expressed in cochlear glia-like supporting cells (GLSs) have never been clearly associated with progressive deafness. Herein, we present a novel deafness locus mapped to chromosome 3p25.1 and a new auditory neuropathy spectrum disorder (ANSD) gene TMEM43 mainly expressed in GLSs. We identify p.R372X of TMEM43 by linkage analysis and exome sequencing in two large Asian families. The knock-in (KI) mouse with p.R372X mutation recapitulates a progressive hearing loss with histological abnormalities exclusively in GLSs. Mechanistically, TMEM43 interacts with Cx26 and Cx30 gap junction channels, disrupting the passive conductance current in GLSs in a dominant-negative fashion when the p.R372X mutation is introduced. Based on the mechanistic insights, cochlear implant was performed on two patients and speech discrimination was successfully restored. Our study highlights a pathological role of cochlear GLSs by identifying a novel deafness gene and its causal relationship with ANSD. Copy rights belong to original authors. Visit the link for more info

Dr. Neera K. Dahl, MD, PhD, a leading nephrologist at Yale School of Medicine who specializes in diagnosing and treating kidney ailments and genetic kidney disorders such as ADPKD, shares important information on ADPKD and living with the condition. She also helps educate patients on how accepting their diagnosis and learning to manage their symptoms can help them take charge of their life with ADPKD. Dr. Neera Dahl, here on behalf of Otsuka America Pharmaceutical, Inc.

Have you considered doing an autosomal DNA test to add to and improve the accuracy of your family tree? Have you ever heard of autosomal DNA? It is the most common type of publicly available DNA test nowadays and is quite affordable. Here is what you need to know about this valuable genealogical DNA test. Show Notes: https://ancestralfindings.com/y-dna-and-mt-dna-and-how-they-can-help-you-trace-your-ancestors/ Listen to the Weekly Podcast: https://ancestralfindings.com/podcast Weekly Giveaways: https://ancestralfindings.com/drawing  Free eBooks: https://ancestralfindings.com/ebooks  Hard To Find Surnames: https://ancestralfindings.com/surnames  Social Media: https://www.twitter.com/ancestralstuff  https://www.facebook.com/AncestralFindings https://www.instagram.com/ancestralfindings  #DNA #Genealogy #AncestralFindings

This form is much more severe. Here we will talk about the causes and it’s many effects on the skeletal, blood, nervous, immune and endocrine system.

Here we go in depth about genetic mutations, specific genetic malfunctions associated with Autosomal Dominant Osteopetrosis, and it’s localized effects on the bones. This is also the most commonly diagnosed form of the disease and has less severe effects on the entire body. The next episodes will show how more severe manifestions of the disease effect much more than just the skeletal system.

An introduction to DNA and genetic genealogy.

Session 07 We often associate biochemistry with undergrad, but biochemistry is present in many specialties! Let’s dive into the types of biochem questions you may see! We're joined once again by Dr. Andrea Paul from Board Vitals as we help you prepare for your first board exam so you have what it takes to score high and match into your specialty of choice. Use the promo code BOARDROUNDS to save 15% on your QBank purchase. [03:30] Why Biochemistry? Biochemistry is more applicable to some specialties than others. But just basic genetics and metabolic diseases, for instance, are seen in many specialties. Biochemistry comes into play especially when you talk about metabolic diseases. Hence, it's a commonly tested subject on the exam, more than the other basic science components. [04:41] Question for this Week: A healthy married couple has a child who develops clinical symptoms of what you suspect to be a rare disease. Genetic testing revealed the patient's mother carries the mutated gene, but the father is not a carrier. However, the father's brother had the same disease, which has also occurred in one of his sisters' sons. This pattern is characteristic of which of the following diseases? Note from Andrea: The question is drawing you a pedigree. You can jot down a little diagram of pedigree for yourself as you're going through it. You have to figure out the pattern from the pedigree but know which diseases of the options fit that pattern of inheritance. Answer choices: (A) G6PD (B) Cystic fibrosis (C) Phenylketonuria (PKU) (D) Alpha-1 antitrypsin deficiency (E) Tay-Sachs Disease [05:50] The Thought Process Behind the Answer Once you've drawn that pedigree and determined what the inheritance pattern is, you can go through each option and cross out what doesn't fit or jot down what pattern each one has. In this case, the couple is healthy and not showing any disease. But the one child does and the father is not a carrier. This gives you another hint. So if he's not a carrier, how is that possible if the child is showing the disease? Then you're seeing that it's present in the father's brother and one of the sisters' sons. Here, you can see a distinctive pattern where this is not an autosomal recessive type pattern. This leads you to a dominant X-linked route. As you draw this out, you will start to see the pattern where the children follow up to them. The mother is a carrier, the father is not. And the child has the disease. It's likely that the child is a male because they're receiving only an X from the mom. So this would be an X-linked pattern. Now, you would only see one that follows that X-linked disease – G6PD Looking at patterns and pedigrees can really help you. Another algorithm Andrea found helpful is to ask: does the child with the disease have a parent with a disease. If no, then you're skipping a lot of things. You're left here with X-linked recessive which is 50% more common than a male child. Therefore, it's an X-linked recessive disease. [11:02] Tips and Tricks to Help You Memorize and Understand Better Most students are using mnemonics to remember all of the X-linked recessive diseases. This is most common for autosomal recessive or autosomal dominant. There's no way to think through them in a way that doesn't require memorization. The names of the disease don't really help in this case. All this being said, Andrea recommends using mnemonics. You can also use visual mnemonics you can look at or silly drawings to help you remember stuff. [12:37] Other Possible Questions Probably, if the question talked about a food that this person that this person may develop symptoms with, then you could probably remove some answer choices out. For example, G6PD is one of those diseases. If it's cystic fibrosis, they could ask what microbe commonly infects patients with this disorder. Or they could ask a treatment for that disorder. [14:00] Other Patterns Students Should Know About One pattern would be X-linked dominant. In this case, you would not see skipping of generations unlike what's in the above question. You would also see male and female as affected equally since the disease of the X chromosomes is dominant. So you think of diseases like X-linked dominant Alport syndrome or hypophosphatemic rickets. Another interesting inheritance pattern is mitochondrial where males and females are affected equally. It would skip generations but it is only transmitted from an affected female because mitochondrial diseases come from the maternal side always. And you would see a different pattern and all of the offspring would be affected – something you wouldn't see in the other types. Autosomal dominant, you would also see male and female as affected and not skipping generations. For instance, if two parents without the disease have a child with the disease, you'd think that the only way this could be autosomal dominant is there's a new mutation or there's some type of reduced penetrants or maybe the parent has the gene but just phenotypically normal. Otherwise, you would see this in every offspring because it's a dominant disease. Autosomal recessive is the opposite where you see skipping of generations. For example, if you have a couple both carrying the gene without any signs of disease, there would be 25% the child is born with two normal genes from the parents, 50% chance that they have one normal and one abnormal gene, and 25% that they would receive both. Since it's recessive that's the only case where you would see disease such as cystic fibrosis, thalassemia, sickle cell anemia, or PKU (of which some are shown in the answer choices above). Spinal muscular atrophy would be a more popular disease here, which my daughter has but me and my wife don't have, which makes us both carriers. This is going to be more popular to start talking about it on medical school and the boards because it's one of the first diseases out there that will be cured with gene therapy. [17:45] Board Vitals If you're interested in the QBank and how Board Vitals can help you prepare the best way you can for your Step 1 or Level 1, check out their site and use the promo code BOARDROUNDS to save 15% off of your QBank purchase. Links: Board Vitals (promo code: BOARDROUNDS)

Jori and Dan have a very unique son named Luxton.  He is one of three cases in the world that has autosomal recessive centronuclear myopathy type 5. Luxton however is the only one in the world that has two mutated genes. Autosomal Recessive Centronuclear Myopathy Type 5: The Only One Something Was Wrong Luxton’s doctors knew there was something wrong right off the bat.  However, no one really knew what it was. “He couldn’t breathe on his own, they called a code blue.” Jori recalls.   She continues by saying, “ They had a laundry list of things they thought it could be.  His MRI showed some brain bleeds. They thought he had Gyneschemic brain injuries because he did have a rough delivery so he was restricted in utero.” “It’s Terminal, Whatever he Has” At three weeks old his oxygen dropped to the 20’s and Jori and Dan were unable to find a pulse.  They were admitted for three months on and off and the doctors were still not able to find out what was wrong.  “It’s terminal whatever he has.  So don’t expect him to look at you, don’t expect him to laugh.  He’s never going to play with toys. He’s never going to walk, he;s never going to crawl, he’s never going to sit up, he’s going to be a vegetable.”  Official Diagnosis at 16 Months After 16 long months, they received a test called a microarray.  The test showed small deletion on chromosome two. “Well we got the diagnosis and I remember the lady walking in the room.  She was like “so we found something this is a gene it affects but we have no other records of this being found”  “The other two records that are very similar is both kids are trach vented and doctors said that they don’t have a very good prognosis” I was devastated” Jori mentioned.   “Just be his Mom” In the first couple months of Luxton’s life Jori was struggling, she was feeling sad, guilty, jealous and like she couldn’t do it.  Dan put things in perspective for her by saying “Jori stop listening to the doctors, stop looking at everything they are telling you is wrong and just be his mom.” “I stopped looking at what he’s never going to do and what everyone's labeling my child as and once I stopped doing that,  was able to pay attention to what he can do… and then I started getting joy out of that.” He’s Proving Doctors Wrong “He does things they told us he would never even do..he rolls and now he is lifting his head up off the ground...he does things that other moms don’t get to experience, we just have a very special bond.” said Jori. Dan loves Luxton's happy personality, he said, “I love coming home and seeing him dance around me and get excited.  It’s really wonderful having him be part of our family. He just seems to have this determination to never really give up.”

Commentary by Dr. Valentin Fuster

Randall Bateman and Nick Fox discuss what they've learned from their papers on Alzheimer's disease.

Veterinary Pathology podcast editor Leah Schutt discusses the the article, "Autosomal Recessive Congenital Ichthyosis in American Bulldogs Is Associated With NIPAL4 (ICHTHYIN) Deficiency" with Dr. Mauldin and Dr. Casal, two of the authors of the study. To view this article, click here.

A lawyer, a filmmaker, a host and a comedian serve a cocktail made up of the basic ingredients: Fame, Marriage, Genetics and Hotties. This episode they discuss why everyone wants to be famous; has social media made marriage obsolete; where do we come from; and #MCM & #WCM flirtatious or foolhardy . If you consider yourself a conversational mixologist, then hit play, until the bartender cuts you off. Why does everyone want to be famous: http://www.huffingtonpost.com/donna-rockwell-psyd/mindfulness-in-everyday-l_2_b_4818606.html Is Marriage Obsolete: http://www.pbs.org/thisemotionallife/blogs/does-internet-promote-or-damage-marriage Where do we come from: http://www.pbs.org/thisemotionallife/blogs/does-internet-promote-or-damage-marriage Freedman's Beaureau records to be available online: http://www.vibe.com/2015/06/african-american-family-records-from-slavery-era-will-be-available-online-for-free/ #MCM & #WCW: http://www.urbandictionary.com/define.php?term=%23MCM & http://www.urbandictionary.com/define.php?term=WCW

Have you had your autosomal DNA tested and now you are confused?  Allow Diahan Southard to explain how you can organize, analyze and understand your results. In the year 2000 Diahan Southard found herself in the right place at the right time.  As an undergraduate in Microbiology, the laboratory she had been volunteering in was headed to Egypt to collect more samples for genetic study from an abandoned cemetery just outside of Cairo. While that trip never materialized, that research study became the foundation of the Sorenson Molecular Genealogy Foundation (SMGF), for whom she would work for the next 10 years. Her duties at SMGF and her sister companies were varied, from laboratory work to marketing to customer service. All of her knowledge and experience have culminated into her current position as Your DNA Guide. She writes for Family Tree Magazine, and is the Genetic Gem at Lisa Louise Cooke’s Genealogy Gems, blogging and podcasting about DNA and genealogy. Diahan's lectures are always fun, upbeat, and full of energy.  She has a passion for genetic genealogy, a genuine love for people, and a gift for making the technical understandable. guide@yourDNAguide.com www.yourDNAguide.com  

We all need a little inspiration now and then, and in this episode I hope to bring you some through good books, inspiring comments from other listeners, and some new ideas to try. Once I got past the organization of my new office, what I've really enjoyed doing is devoting time to display family photos and artifacts, and just decorating the room. It may seem frivolous, but I don't this it is. We spend a lot of time in our offices, and you may have a home office, or corner of a room where you work on your genealogy.  Considering the importance of the work and the time you spend doing it, I think it's time and effort well spent to put effort in to inspiring decorations and displays.  (Lisa's new office display)   MAILBOX: Feedback on the “Lizzie” interview from AlvieI am thoroughly enjoying the podcasts and videos. Recently I drove to South Florida and listened to the episode about Lizzie Milligan.  It sure brought back lots of memories.  Many years before I got heavy into genealogy a co-worker of mine gave me a large box of post cards which was passed to him by his grandmother.  These cards were mailed during the digging of the Panama Canal and these were cards sent to his grandmother by her future husband from Panama. They were so very interesting reading but I had no use for them so I turned them over to our local museum in Lakeland, FL.  I don't know what became of them.   Kay loves MyHeritage too "Loved this podcast today - I listened while I walked my 3-mile loop.  Just want to share a MyHeritage story. I had uploaded a small GEDCOM at least a couple of years ago and never done much with it.  They had no record matching to speak of in the beginning and all the family matches were to persons who had much less information about the families than I did.   However, at RootsTech last winter, I talked to one of their reps - told him I would probably just let my subscription run out.  He convince me to try uploading a larger file, get the data subscription, and in fact offered me a free three months to try again - so I really couldn't say no. Now a bit of background.  I lived in Alabama for several years - and probably about 15 years ago the newspaper had published an extended article about the Sultanadisaster, the steamboat that exploded on the Mississippi River near Memphis on 27 Apr 1865 with the loss of some 1600 lives  - the Cahaba prison where so many of those unfortunate men on the Sultana had come from was only about 50 miles from us.  At that point I'd never heard of it but I became quite fascinated and interested in the story and read everything I could find - I discovered that most of the released Union prisoners who died on the Sultana were from Indiana, Illinois & Ohio and knew that I had family in Indiana during that War, but didn't think there was any personal connection. After I began to work with MyHeritage again, up popped a Kokomo Daily Tribunenewspaper obituary of the brother-in-law of one of my paternal great-grandfathers, who had died in 1925 in Howard County, IN.   And there it was - he had been on theSultana and had suffered serious burns the result of which remained problematic for the rest of his long life.  It was thought that infection from the old burn wounds were the ultimate cause of his death.  In fact, he had been reported as dead to his family, because of the unbelievable chaos that surrounded the rescues.   What joy there must have been when he did return home! I always wonder when this sort of serendipity happens.  Was I always fascinated by this saga because I knew that somehow there was a family story involved? Anyway, I, too have become a believer in MyHeritage!  The brother-in-law never applied for a pension, or otherwise mentioned his service and I had the information about where he was buried.  As a collateral relative, he wasn't really a person I spent much research time on.   I probably never would have done a thorough newspaper search.  But there it was - nicely found for me and connecting to another bit of history!"     GEM: BOOK CLUB conversation with Sunny Morton “When [your] parent dies…your relationship with their history changes almost overnight. It suddenly becomes much more relevant to you because you feel like you are the only one left who is in a position to remember it. So having never wanted to know anything about my mother's life, suddenly after her death it seemed imperative to me to find out absolutely everything….It felt to me that I couldn't…stake out the parameters of what I'd lost until I knew everything there was to know about her.” -Emma Brockes, on She Left Me the Gun  Book Recommendations: Suggestion from Mary:  by Mani Feniger Here's one along a similar theme of secrets in a mother's past and the mother-daughter relationship. One of our listeners, Mary, wrote to us about it. She said, "I just ordered this book and thought you might be interested in reading it. I am looking forward to reading it myself.” The book is The Woman in the Photograph by Mani Feniger. Here's a little blurb on the book: Mani Feniger wanted nothing to do with the relics of her mother's life before she escaped from Nazi Germany in 1936. But when the fall of the Berlin Wall exposed the buried secrets and startling revelations of her mother's past, she was drawn into an exploration-of history and family, individuality and identity, mothers and daughters-that would change her life forever." Listener suggestion from Mike:   is by John Bailey "Here's a book I found that you and your listeners might also enjoy.  recounts the story of a poor emigrant family and what happened to one of the daughters.  I found it fascinating.  The story is non-fiction and takes place around New Orleans in the first half of the 19th century.  There is much family research involved, some heart-wrenching descriptions of what the emigrants suffered, and delightful insights into the New Orleans of that time period.  It's the kind of research that we family historians love to do but is more dramatic than many of the personal stories we work on."   Profile America: Thursday, November 13th “Even the most mundane items we take for granted have to be invented by someone. This month 110 years ago, that someone was Connecticut inventor Harvey Hubbell. In November 1904, he received a patent for the world's first detachable electric plug: the two-, now sometimes three-prong plug familiar to us today. Remarkable as it sounds, at the time electric terminals would extend out from a wall, and any electrical device had to be hardwired to them. A time consuming process with a chance of electrocution. Hubbell was no one-hit wonder, as in the 1890s he created an electric switch and patented the pull-chain electric light socket. Electrical supplies for builders and homeowners are available at nearly 29,000 locations in the U.S., including 6,500 home centers and 12,500 hardware stores.”     Improvements in Using Autosomal DNA for GenealogyDiahan Southard, Your DNA Guide You may recall from our recent DNA discussion on the Genealogy Gems podcast () that Ancestry.com recently discontinued their mtDNA and YDNA tests (the two that trace our direct maternal and direct paternal lines) to focus on autosomal DNA (which delivers information about both your mother's and your father's side of your ancestral tree). Well, recently I attended an all-day meeting hosted by Ancestry.com: a summit to talk about current trends and accomplishments at Ancestry DNA , and ideas about the future of DNA testing at Ancestry.com.  The meeting included a diverse group of Ancestry representatives, from CEO Tim Sullivan to members of the marketing, scientific, communications, and even computer science departments, as well as some of the top voices in genetic genealogy. It was an open and lively discussion, and I walked away with a few gems I want to share with you today. More Powerful DNA Hints Coming In AncestryDNA, the ‘shaky leaf” hints are meant to help you find a common ancestor between you and your DNA matches. The computer code behind the old hints was not very efficient. Lazy, in fact. It started at the bottom of your tree—and the bottom of your match's tree—and slapped on a shaky leaf at the first sign of a shared common ancestor. While this method worked for a large number of cases, it was leaving a lot of stones unturned. But the IT guys at Ancestry have beefed up the computer power, allowing them to cover a much greater distance through our trees and the trees of our matches before making a judgment about the best place to assign that shaky leaf. The result? Better hints about how you and your match COULD be related. Remember, the leaf is still just a SUGGESTION on how you and your match might be related. It is not a crystal ball. Did You Know? Ancestry DOES store your DNA samples in a secure location. Ancestry spent months designing their own DNA collection kit. Ancestry was able to attract some of the brightest scientists in the field of population genetics because of YOU. You with your documented pedigree charts and your willingness to help move this science of discovering our ancestors forward. Looking Ahead There is no question that the genetic genealogy industry is rapidly advancing, and our discussion with Ancestry certainly didn't disappoint. While I will be sharing with you in future posts about some of the exciting changes, I do want you to be ready for one that will be coming online fairly soon. It has to do with your matches. If you have been tested by AncestryDNA, you may have been initially excited, then nearly immediately overwhelmed, by the number of individuals listed in your match page, all claiming to have some kind of connection to you and your family tree. All three major genetic genealogy testing companies (AncestryDNA, Family Tree DNA, and 23andMe) are using basically the same laboratory methods to glean information from your DNA. What differs is how they use that data to draw conclusions about your ethnic heritage and about your relationships to other individuals. As it turns out, AncestryDNA has been reporting far more individuals as your relatives than it should have. You can think of it like this: You have sent out tickets, in the form of your genetic code, to an exclusive party where you (of course!) are the star. However, you have lost the guest list and you are counting on the testing company to check the ticket of each guest before they enter your party to be sure they were really invited. AncestryDNA was relatively new in the role of party bouncer, and in the interest of not turning away any VIP guests, they initially allowed guests into your party who had (gasp!) forged tickets!! But as AncestryDNA admits more guests, the experience it's gained in party monitoring is starting to show. You see, each of the forged tickets has some unique qualities that have started to send up red flags to the team of scientists at AncestryDNA . They are now in the process of carefully documenting what each forged ticket looks like and tossing those unwanted guests out on their ear. The short of it: in the near future your match list at Ancestry will be much shorter. Which is good news to you, as it means only those invited genetic cousins will be around eating hors d' oeuvres and ready to talk about your shared common ancestry. Each testing company has its strengths and weaknesses. It was good to have a bit of insight into this one company and come to a greater understanding about why it is they do what they do. It is a great time to be in this young genetic genealogy industry, with so much room to grow and change. I will let you know when I find the next genetic gem. Use our affiliate link / ad to get free shipping and help support the free podcast.   GEM: Couple Celebrates 80 years of Marriage Read  Watch the video and see photos through time of the successful couple at       

CeCe Moore and Shannon Christmas will discuss strategies for using autosomal DNA to resolve your genealogical problems. CeCe Moore is a professional genetic genealogist and writes the popular blog Your Genetic Genealogist, where she covers the developments in the field of DNA genealogy as an independent, unbiased authority. She is the Southern California Regional Coordinator for the International Society of Genetic Genealogy and the administrator of the organization’s DNA Newbie Mailing List.  CeCe is also the genetic genealogy consultant for Finding Your Roots with Henry Louis Gates Jr. Season Two and Genealogy Roadshow and she also ls the administrator of the Hemings-Jefferson Autosomal DNA Project. Shannon Christmas is an experienced genealogist specializing in genetic, colonial American, and African-American genealogy in Virginia and the Carolinas. He serves as a 23andMe Ancestry Ambassador, an Ancestry.com Ace, administrator of The Captain Thomas Graves of Jamestown Autosomal DNA Project, and a co-administrator of The Hemings-Jefferson-Wayles-Eppes Autosomal DNA Project. 

  CeCe Moore and Shannon Christmas will discuss strategies for using autosomal DNA to resolve genealogical problems. CeCe Moore is a professional genetic genealogist and writes the popular blog Your Genetic Genealogist, where she covers the developments in the field of DNA genealogy as an independent, unbiased authority. She is the Southern California Regional Coordinator for the International Society of Genetic Genealogy and the administrator of the organization’s DNA Newbie Mailing List. In 2012, CeCe was personally appointed by the CEO of 23andMe to serve as their lead Ancestry Ambassador, a volunteer position that enables her to promote the interests of the genealogy community. Shannon Christmas is an experienced genealogist specializing in genetic, colonial American, and African-American genealogy in Virginia and the Carolinas. He serves as a 23andMe Ancestry Ambassador, an Ancestry.com Ace, administrator of The Captain Thomas Graves of Jamestown Autosomal DNA Project, and a co-administrator of The Hemings-Jefferson-Wayles-Eppes Autosomal DNA Project.      &

Background: Mutations in SACS, leading to autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), have been identified as a frequent cause of recessive early-onset ataxia around the world. Here we aimed to enlarge the spectrum of SACS mutations outside Quebec, to establish the pathogenicity of novel variants, and to expand the clinical and imaging phenotype. Methods: Sequencing of SACS in 22 patients with unexplained early-onset ataxia, assessment of novel SACS variants in 3.500 European control chromosomes and extensive phenotypic investigations of all SACS carriers. Results: We identified 11 index patients harbouring 17 novel SACS variants. 9/11 patients harboured two variants of at least probable pathogenicity which were not observed in controls and, in case of missense mutations, were located in highly conserved domains. These 9 patients accounted for at least 11% (9/83) in our series of unexplained early onset ataxia subjects. While most patients (7/9) showed the classical ARSACS triad, the presenting phenotype reached from pure neuropathy (leading to the initial diagnosis of Charcot-Marie-Tooth disease) in one subject to the absence of any signs of neuropathy in another. In contrast to its name ``spastic ataxia{''

Vincent, Alan, and Matt discuss herpes simplex encephalitis in children with innate immune deficiency, and the local response to microneedle-based influenza skin immunization. Links for this episode: Herpes encephalitis in children with TRIF deficiency (J Clin Inv) Toll-like receptor and cytosolic pattern recognition receptors Skin responses to influenza microneedle vaccine (mBio) Microneedles Fluzone intradermal influenza vaccine QDot nanocrystal technology TWiV on Facebook Letters read on TWiV 175 Weekly Science Picks Matt - Phage and the Origins of Molecular BiologyAlan - Digital Imagine InstituteVincent - iPad apps Goodreader and Notability Listener Pick of the Week Jane -Smoking Ears and Screaming Teeth by Trevor Norton

Thu, 17 Nov 2011 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/13673/ https://edoc.ub.uni-muenchen.de/13673/1/Hendrich_Saskia.pdf Hendrich, Saskia Anneliese Dorothea

Sun, 13 Nov 2011 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/16690/ https://edoc.ub.uni-muenchen.de/16690/1/Klein_Pontus.pdf Klein, Pontus ddc:570, ddc:500, Fakultä

In this episode we explore using autosomal DNA testing to solve family mysteries, planning a research trip to Salt Lake City and more.

Das autosomal-dominante Hyper-IgE-Syndrom (AD-HIES) gehört zu den angeborenen Immundefekten und wird durch Ekzem, erhöhtes Serum-IgE, Eosinophilie, rezidivierende Abszesse und Lungeninfektionen sowie assoziierte Skelett- und Bindegewebssymptome charakterisiert. Durch die Assoziation von Mutationen im Gen STAT3 bei Patienten mit AD-HIES gelang es 2007 die ätiologische Ursache dieses Krankheitsbildes aufzuklären, wodurch die Diagnose heute molekulargenetisch bestätigt werden kann (Holland et al. 2007; Minegishi et al. 2007). Ziel der vorgelegten Arbeit war es, den klassischen AD-HIES-Phänotyp mit dem STAT3-Genotyp zu korrelieren und die bestmöglichen Kriterien zu definieren, die Patienten mit STAT3-HIES charakterisieren und eine Abgrenzung zu ähnlichen Erkrankungen (z.B. atopische Dermatitis) sowie eine frühzeitige Diagnose ermöglichen. Hierfür wurden 78 Patienten mit unterschiedlich ausgeprägtem HIES-Phänotyp auf eine Mutation in STAT3 untersucht. Der Phänotyp der Patienten wurde anhand des NIH-Scores quantitativ beurteilt, der die Wahrscheinlichkeit für ein HIES bestimmt (≥40 Punkte entsprechen der klinischen Diagnose HIES) (Grimbacher et al. 1999b). Bei 48 der untersuchten Patienten konnte eine heterozygote Mutation in STAT3 identifiziert werden. Es handelte sich um 24 verschiedene Mutationen, darunter 19 Erstbeschreibungen, die in drei funktionellen Domänen des STAT3 Proteins auftraten. Alle Mutationen erlauben die Expression eines veränderten STAT3 Proteins, das einen dominant-negativen Effekt auf die STAT3 Funktion ausübt (Minegishi et al. 2007; Renner et al. 2008). 96% der Patienten mit STAT3 Mutation (STAT3-mut Patienten) hatten ≥40 Punkte im NIH-Score und dementsprechend die klinisch-gesicherte Diagnose eines HIES. Bei 30 Patienten wurde auf genomischer DNA-Ebene keine Mutation in STAT3 gefunden (STAT3-wt Patienten); 90% gehörten der Gruppe der „Verdacht auf HIES“-Patienten an (85% Spezifität): Organabszesse, schwere Infektionen (Sepsis, Meningitis, Osteomyelitis), Pneumatozelen, Frakturen ohne adäquates Trauma, Skoliose und Nagel/mukokutane Candidiasis. Funktionell spielt STAT3 eine wichtige Rolle bei der Differenzierung von IL-17 produzierenden CD4+-T-Zellen (TH17-Zellen), die bei der Abwehr von extrazellulären Bakterien und Pilzen beteiligt sind (Yang et al. 2007; Ochs et al. 2009). Diese Arbeit konnte bestätigen, dass STAT3-mut Patienten signifikant erniedrigte TH17-Zellen im Vergleich zu STAT3-wt Patienten und normalen Kontrollen haben. Zum einen kann hiermit die Abwehrschwäche gegenüber Staphylococcus aureus und Candida albicans erklärt werden, zum anderen stellen die TH17-Zellen einen sehr sensitiven und spezifischen diagnostischen Marker für ein STAT3-HIES dar. Aus der Literatur ist außerdem bekannt, dass STAT3-Signalwege eine wichtige Rolle bei der Differenzierung von Osteoblasten und Osteoklasten spielen, und für die Aufrechterhaltung der Knochenhomöostase von Bedeutung sind (O'Brien et al. 1999; Itoh et al. 2006). Daraus ergibt sich eine mögliche Erklärung für die Skelett- und Bindegewebsanomalien bei STAT3-HIES Patienten, die aufgrund einer verminderten STAT3-Proteinfunktion entstehen können. Basierend auf den klinischen und immunologischen Korrelationsanalysen wurde der NIH-Score in den vereinfachten 5-Punkt-Score weiter entwickelt, der keine qualitative Wertung der Ausprägung und Häufigkeit der Symptome enthält (vergl. Tabelle 12). Die retrospektive Erhebung des 5-Punkt-Scores erzielte in dieser Studie eine vergleichbar hohe Korrelationsrate wie der NIH-Score (vergl. Tabelle 13). Zusammen mit der TH17-Zellzahlbestimmung stellt der 5-Punkt-Score ein diagnostisches Hilfsmittel für STAT3-HIES dar, ohne dem NIH-Score überlegen zu sein. Die Erkenntnisse dieser Studie liefern einen wichtigen Beitrag zur klinisch-genetischen Definition des STAT3-assoziierten HIES und stellen wesentliche Kriterien, die zur Diagnosefindung und Abgrenzung klinisch ähnlicher Erkrankungen führen, dar. Durch eine frühzeitige Diagnosestellung wird schließlich die Einleitung einer adäquaten Therapie ermöglicht, durch die Komplikationen vermieden und die Lebensqualität sowie Prognose der Patienten deutlich verbessert werden können. Weitere Untersuchungen von Zusammenhängen zwischen STAT3-Mutationen, der STAT3-Proteinfunktion und der Entstehung der einzelnen Symptome können in Zukunft neue Therapieansätze generieren und wichtige Erkenntnisse über die Entstehung von eigenständigen Erkrankungen wie der Osteoporose, der idiopathischen Skoliose oder Erkrankungen aus dem atopischen Formenkreis liefern.

Thu, 15 Oct 2009 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/11246/ https://edoc.ub.uni-muenchen.de/11246/1/Pawlita_Ingo.pdf Pawlita, Ingo

An Interview with Monique Ryan, M Med, BS, FRACP and Robert Ouvrier, MD, BS, BSc, coauthors of Autosomal-recessive and X-linked forms of hereditary motor and sensory neuropathy in childhood. Muscle Nerve 2007;36:136-143. Interviewed by Ted Burns.

An Interview with Monique Ryan, M Med, BS, FRACP and Robert Ouvrier, MD, BS, BSc, coauthors of Autosomal-recessive and X-linked forms of hereditary motor and sensory neuropathy in childhood. Muscle Nerve 2007;36:136-143. Interviewed by Ted Burns.

Autosomal-Recessive and X-linked Forms of Hereditary Motor and Sensory Neuropathy in Childhood by Monique Ryan, M Med, BS, FRACP and Robert Ouvrier, MD, BS, BSc

The regulation of phosphate metabolism is a complex process that is still only partly understood. At the end of the eighties, studies in a mouse model for hypophosphatemic rickets provided evidence that phosphate wasting could not be explained by a primary defect of the kidney but rather by an unknown circulating factor with phosphaturic properties. X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets (ADHR), and tumor induced osteomalacia (TIO) are three well defined human disorders of isolated renal phosphate wasting. XLH and ADHR are mendelian diseases while TIO is caused by rare, mostly benign tumors. The opposite phenotype, hyperphosphatemia due to increased renal phosphate reabsorption is associated to the recessive disorder familial tumoral calcinosis (FTC). At the beginning of this work the genes mutated in XLH and ADHR were cloned. One gene codes for the endopeptidase PHEX, the other for the fibroblast growth factor FGF23. Both proteins are probably involved in a novel common pathway of the regulation of phosphate homeostasis. Missense mutations in FGF23 causing phosphate wasting in patients with ADHR, overexpression of FGF23 in tumors from patients with TIO, and the observation that FGF23 plasma levels are elevated in most patients with XLH provided strong evidence that FGF23 is a hormone with phosphaturic activity. However, the function of FGF23 in the regulation of phosphate metabolism is far from understood. The intention of this study was to investigate the molecular properties of native FGF23 and its mutant forms. I conducted protein expression experiments in HEK293 cells which showed that native FGF23 is a secreted protein partially processed into an N-terminal fragment and a C-terminal fragment. I provided evidence that this cleavage occurs during protein secretion and it is performed by subtilisin like-proprotein convertases (SPCs). In addition, I determined that native FGF23 undergoes O-linked glycosylation before secretion by using a deglycosylation assay. Further, RT-PCR analysis of human tissues showed FGF23 expression in whole fetus, heart, liver, thyroid/parathyroid, small intestine, testis, skeletal muscle, differentiated chondrocytes and TIO tumor tissue. In mouse, FGF23 was expressed in day 17 embryo and spleen. The FGF23 ADHR mutations replace arginine residues at the SPC cleavage site (RXXR motif). By expression of the FGF23-R176Q and –R179Q mutant proteins in HEK293 cells I showed that ADHR mutations prevent cleavage at the RXXR site and stabilize FGF23. This alteration in the FGF23 cleavage enhances FGF23 phosphaturic activity in ADHR. Familial tumoral calcinosis (FTC) with hyperphosphatemia is a disease considered the mirror image of the hypophosphatemic condition. It is known that FTC is caused by mutations in the GALNT3 gene. By performing mutation analysis in two families with FTC, I could show that FTC can also be caused by inactivating mutations in the FGF23 gene. To characterize the FGF23-S71G mutant protein I conducted in vitro expression assays, immunocytochemistry and ELISA to measure the FGF23 plasma levels in the patient with FTC. Taken together the results of these experiments showed that intact FGF23-S71G mutant protein remained inside the cells and only the C-terminal FGF23 fragment was secreted. These investigations demonstrate that FGF23 mutations in ADHR and FTC have opposite effects on phosphate homeostasis. There is evidence that the endopeptidase PHEX which is mutated in patients with XLH and FGF23 act in the same pathway. PHEX function resides upstream of FGF23 and may be involved in the degradation of FGF23 thereby regulating its phosphaturic activity. I designed an assay with a recombinant secreted form of PHEX (secPHEX) to prove whether FGF23 is a substrate of PHEX. Although secPHEX activity could be demonstrated by degradation of PTHrP107-139, secPHEX failed to degrade FGF23 in this assay. These results provided evidence against a direct interaction of PHEX and FGF23.

A unique sutural cataract was observed in a 4-generation German family to be transmitted as an isolated autosomal, dominant trait. Since mutations in the gamma-crystallin encoding CRYG genes have previously been demonstrated to be the most frequent reason for isolated congenital cataracts, all 4 active CRYG genes have been sequenced. A single base-pair change in the CRYGA gene has been shown, leading to a premature stop codon. This was not observed in 170 control individuals. However, it did not segregate with the disease phenotype. This is the first truncating mutation in an active CRYG gene without a dominant phenotype. As the CRYGA mutation did not explain the cataract, several other candidate loci (CCV, GJA8, CRYBB2, BFSP2, MIP, GJA8, central pouch-like, CRYBA1) were investigated by micro-satellite markers and linkage analysis, but they were excluded based on the combination of haplotype analysis and two-point linkage analysis. The phenotype in this family is due to a mutation in another sutural cataract gene yet to be identified.

Autosomal recessive mutations in the 17 beta-hydroxysteroid dehydrogenase 3 gene impair the formation of testosterone in the fetal testis and give rise to genetic males with female external genitalia. Such individuals are usually raised as females, but virilize at the time of expected puberty as the result of increases in serum testosterone. Here we describe mutations in 12 additional subjects/families with this disorder. The 14 mutations characterized to date include 10 missense mutations, 3 splice junction abnormalities, and 1 small deletion that results in a frame shift. Three of these mutations have occurred in more than 1 family. Complementary DNAs incorporating 9 of the 10 missense mutations have been constructed and expressed in reporter cells; 8 of the 9 missense mutations cause almost complete loss of enzymatic activity. In 2 subjects with loss of function, missense mutations testosterone levels in testicular venous blood were very low. Considered together, these findings strongly suggest that the common mechanism for testosterone formation in postpubertal subjects with this disorder is the conversion of circulating androstenedione to testosterone by one or more of the unaffected 17 beta-hydroxysteroid dehydrogenase isoenzymes.

Pseudohypoaldosteronism type 1 (PHA1) is an uncommon inherited disorder characterized by salt-wasting in infancy arising from target organ unresponsiveness to mineralocorticoids. Clinical expression of the disease varies from severely affected infants who may die to apparently asymptomatic individuals. Inheritance is Mendelian and may be either autosomal dominant or autosomal recessive. A defect in the mineralocorticoid receptor has been implicated as a likely cause of PHA1. The gene for human mineralocorticoid receptor (MLR) has been cloned and physically mapped to human chromosome 4q31.1-31.2. The etiological role of MLR in autosomal recessive PHA1 was investigated by performing linkage analysis between PHA1 and three simple sequence length polymorphisms (D4S192, D4S1548, and D4S413) on chromosome 4q in 10 consanguineous families. Linkage analysis was carried out assuming autosomal recessive inheritance with full penetrance and zero phenocopy rate using the MLINK program for two-point analysis and the HOMOZ program for multipoint analysis. Lod scores of less than -2 were obtained over the whole region from D4S192 to D4S413 encompassing MLR. This provdes evidence against MLR as the site of mutations causing PHA1 in the majority of autosomal recessive families.

Polycystic kidney disease is an inherited disorder where clusters of cysts develop within the kidneys, causing the kidneys to enlarge and lose function over time. The cysts, which are noncancerous sacs containing fluid, vary in size, and they can grow to be large. This disorder can occur in children and adults.The two main types of polycystic kidney disease, caused by different genetic flaws, are: Autosomal dominant polycystic kidney disease (ADPKD). Signs and symptoms of ADPKD often develop between the ages of 30 and 40. In the past, this type was called adult polycystic kidney disease, but children can develop the disorder.Only one parent needs to have the disease for it to pass to the children. If one parent has ADPKD, each child has a 50% chance of getting the disease. This form accounts for most of the cases of polycystic kidney disease.  Autosomal recessive polycystic kidney disease (ARPKD). This type is far less common than is ADPKD. The signs and symptoms often appear shortly after birth. Sometimes, symptoms don't appear until later in childhood or during adolescence.Both parents must have abnormal genes to pass on this form of the disease. If both parents carry a gene for this disorder, each child has a 25% chance of getting the disease. Polycystic kidney disease also can cause cysts to develop in the liver and elsewhere in the body. The disease can cause serious complications, including high blood pressure and kidney failure.The disease varies greatly in its severity, and some complications from polycystic kidney disease are preventable. Lifestyle changes and treatments might help reduce damage to the kidneys from complications, but long-term interventions, including dialysis or kidney transplant, are sometimes needed.On this special Ask the Mayo Mom edition of the Mayo Clinic Q&A podcast, host Dr. Angela Mattke is joined by Dr. Christian Hanna, a pediatric nephrologist with Mayo Clinic Children's Center to discuss PKD in children. Advertising Inquiries: https://redcircle.com/brandsPrivacy & Opt-Out: https://redcircle.com/privacy