Smith Family Clinic for Genomic Medicine’s Post

Parkinson’s disease genes Using linkage analysis,authors identified a new genetic mutation for Parkinson’s disease called RAB32 Ser71Arg. This mutation was linked to parkinsonism in three families and found in 13 other people in several countries, including Canada, France, Germany, Italy, Poland, Turkey, Tunisia, the U.S. and the U.K. Although the affected individuals and families originate from many parts of the world, they share an identical fragment of chromosome 6 that contains RAB32 Ser71Arg. This suggests these patients are all related to the same person; ancestrally, they are distant cousins. It also suggests there are many more cousins to identify. With further analysis, we found RAB32 Ser71Arg interacts with several proteins previously linked to early- and late-onset parkinsonism as well as nonfamilial Parkinson’s disease. The RAB32 Ser71Arg variant also causes similar dysfunction within cells.

Learn how ancestry changes genetic risk variants' impact on type 2 diabetes in childhood cancer survivors & alkylating agent exposure magnifies diabetes risk. https://buff.ly/4bTdE0e #Research #LifeSciences #Health #Biorealty

“SC genotype? “But I thought everyone with sickle cell is SS.” These were the words of a colleague of mine. I saw her surprise at learning about the different genotypes associated with sickle cell disease. It’s a common misconception that all individuals with sickle cell disease have the SS genotype, but in reality, there are several variations. 🧬Sickle Cell Genotypes and Their Meanings: 👉 SS: This genotype occurs when an individual inherits two sickled S genes (one from each parent). It’s the most common and typically associated with the most severe form of the disease. 👉 SC: People with this genotype inherit one S gene and one abnormal hemoglobin called C. This genotype can result in a milder form of sickle cell disease than SS. 👉 Sβ (Beta Thalassemia): This genotype occurs when an individual inherits one S gene and one gene for beta thalassemia, another type of hemoglobin disorder. Why does it even matter to understand these genotypes? ♻ It helps us appreciate the diversity of experiences within the sickle cell community. ♻It allows for more accurate diagnosis and personalised treatment plans. ♻It emphasises the importance of genetic counseling and testing, especially for family planning. I’ll make a different post about other genotypes not directly associated with the symptoms of sickle cell disease. So, turn on your post notifications to learn more. 🔔 Share this post to educate others and help break the stereotypes surrounding sickle cell genotypes. Feel free to ask me any questions you may have in the comments below! 👇

Newly discovered genetic markers help pinpoint diabetes risks, complications . In the largest genome-wide association study to date on Type 2 diabetes, a team of international researchers has located 1,289 genetic markers associated with Type 2 diabetes (145 of which are newly identified) and generated risk scores for diabetes complications. #ScienceDailynews #InnovativeResearch #NextGenScience #ExploringFrontiers

Identifying genes and variants associated with various eye diseases can aid in clinical treatment, as well as in selecting target therapies to reduce the risk of disease reoccurrence in families. Our panels for inherited diseases cover both syndromic and non-syndromic diseases by analyzing a combined 81 different genes. Learn more about our Eye Disorder NGS Panel: https://bit.ly/4cOZChr #retinaldisease #eyedisorder #genetics

In the realm of genetic disorders, Smith-Lemli-Opitz syndrome (SLOS) stands as a challenging puzzle for medical professionals. Ellen Roy Elias, MD, one of the geneticists who helped discover the cause of SLOS, spoke with Rare Disease 360 to shed light on the intricacies of SLOS, its diagnostic journey, treatment options, and the pivotal role of genetic counseling. View the complete article below ⤵️ #SmithLemliOpitzSyndrome #SmithLemliOpitz #GeneticTesting

A recent survey of 2,000 families with Parkinson’s Disease has turned up a new risk factor: a variant in RAB32 Parkinson’s Disease (PD) is a neurodegenerative disease with the majority of cases occurring in people over the age of 60. Early signs of the disease are tremors, difficulty to balance and slowness with dementia, mood swings and behavioral changes presenting at later stages. 85% of cases are sporadic, meaning there’s no family history of disease, and the absolute cause of Parkinson’s is still largely unknown but environmental exposures to certain pesticides, heavy metals, and genetic factors have all been linked to disease. 10-15% of cases are familial or inherited, but even in cases of familial PD it’s been very hard to track down a specific cause of the disease. The molecular hallmark of PD is the development of Lewy bodies in neurons which contain aggregations (clumps) of the protein alpha-synuclein (SNCA) and this clumping is thought to lead to neuronal death. To date, 90 risk variants have been identified along with a few notable genes like SNCA, LRRK2, and PRKN. These genes play a variety of different roles in cells including functioning in cellular metabolism, cell death and protein decay indicating that the cause of PD can be multifaceted. A subset of these mutations have the clinical presentation of PD, but at autopsy do not have SNCA aggregates in neurons. This, of course, adds to the frustration of not knowing how best to treat the disease because most PD research has focused on how SNCA aggregation leads to cell death. There appears to be much more to this story. As for LRRK2 (Leucine-rich repeat kinase 2), it’s a small kinase that phosphorylates a gene called Parkin (PRKN) that’s involved in degrading proteins. Increased activation of LRRK2 is associated with neuronal cell death in cellular and animal models of PD. And while we don’t know exactly how or why this causes PD, the LRRK2/PRKN pathway appears to contribute to the disease in significant ways. That’s why the recent discovery of a new gene involved in PD was so interesting, because it directly impacts the activity of LRRK2. In this research, a family based case-control analysis of 2,184 PD families and 69,775 controls revealed that a variant of RAB32, a protein kinase, was significantly associated with PD (odds ratio 65.5!) In the figure below you can see that this mutant a) results in a significant increase in LRRK2 S1292 phosphorylation and b) associates much more strongly with LRRK2 than the non-mutant. This variant is causal of PD in only about 1% of familial cases, but discoveries like this help us to better understand the molecular mechanisms that lead to PD and offer potential targets for therapeutic development. ### Hop PJ, et al. 2024. Systematic rare variant analyses identify RAB32 as a susceptibility gene for familial Parkinson’s disease. Nature Genetics. DOI: 10.1038/s41588-024-01787-7 --- Want this in your inbox? Visit my website ⬆️

I am pleased to share with you the online webinar document on CRISPR-Cas9.🤗 🌟Genetic disorders occur when a mutation affects your genes. Carrying the mutation doesn’t always mean you’ll end up with a disease. 🌟 There are many types, including single-gene, multifactorial and chromosomal disorders. ❓What are the causes of genetic disorders? When a mutation occurs, it affects the genes’ protein-making instructions. There could be missing proteins. Or the ones you have do not function properly. Environmental factors (also called mutagens) that could lead to a genetic mutation include: ♦️Smoking 🚬 ♦️Chemical exposure ♦️Radiation exposure ♦️UV exposure from the sun ❓How are genetic disorders identified? 🌸 If there’s a family history, DNA testing for genetic disorders can be an important part of starting a family. 🐾Options include: • Carrier testing • Prenatal screening • Prenatal diagnostic testing • Newborn screening ❓How can I prevent a genetic disorder? There is often little you can do to prevent a genetic disorder. But genetic counseling and testing can help you learn more about your risk. It can also let you know the likelihood of passing some disorders on to your children. #online #webinar #certificate #gene_editing #crispr

📃Scientific paper: Differences in Survival across Monogenic Forms of Parkinson's Disease Abstract: International audience; Objective: Survival of patients with monogenic Parkinson's disease may depend on the causative genes associated with the disease. In this study, we compare survival of patients with Parkinson's disease according to the presence of SNCA, PRKN, LRRK2, or GBA mutations.Methods: Data from the French Parkinson Disease Genetics national multicenter cohort study were used. Patients with sporadic and familial Parkinson's disease were recruited between 1990 and 2021. Patients were genotyped for the presence of mutations in the SNCA, PRKN, LRRK2, or GBA genes. Vital status was collected from the National death register for participants born in France. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using multivariable Cox proportional hazards regression.Results: Of the 2,037 patients with Parkinson's disease, 889 had died after a follow-up of up to 30 years. Patients with PRKN (n = 100, HR = 0.41; p = 0.001) and LRRK2 mutations (n = 51, HR = 0.49; p = 0.023) had longer survival than those without any mutation, whereas patients with SNCA (n = 20, HR = 9.88; p < 0.001) or GBA mutations (n = 173, HR = 1.33; p = 0.048) had shorter survival.Interpretation: Survival differs across genetic forms of Parkinson's disease, with higher mortality for patients with SNCA or GBA mutations, and lower mortality for those with PRKN or LRRK2 mutations. Differences in severity and disease progression among monogenic forms of Parkinson's di... Continued on ES/IODE ➡️ https://etcse.fr/yve2 ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

📃Scientific paper: Differences in Survival across Monogenic Forms of Parkinson's Disease Abstract: International audience; Objective: Survival of patients with monogenic Parkinson's disease may depend on the causative genes associated with the disease. In this study, we compare survival of patients with Parkinson's disease according to the presence of SNCA, PRKN, LRRK2, or GBA mutations.Methods: Data from the French Parkinson Disease Genetics national multicenter cohort study were used. Patients with sporadic and familial Parkinson's disease were recruited between 1990 and 2021. Patients were genotyped for the presence of mutations in the SNCA, PRKN, LRRK2, or GBA genes. Vital status was collected from the National death register for participants born in France. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using multivariable Cox proportional hazards regression.Results: Of the 2,037 patients with Parkinson's disease, 889 had died after a follow-up of up to 30 years. Patients with PRKN (n = 100, HR = 0.41; p = 0.001) and LRRK2 mutations (n = 51, HR = 0.49; p = 0.023) had longer survival than those without any mutation, whereas patients with SNCA (n = 20, HR = 9.88; p < 0.001) or GBA mutations (n = 173, HR = 1.33; p = 0.048) had shorter survival.Interpretation: Survival differs across genetic forms of Parkinson's disease, with higher mortality for patients with SNCA or GBA mutations, and lower mortality for those with PRKN or LRRK2 mutations. Differences in severity and disease progression among monogenic forms of Parkinson's di... Continued on ES/IODE ➡️ https://etcse.fr/yve2 ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.