Broad Institute of MIT and Harvard’s Post

🧬Benefits of routine genetic testing in DCM: 👉 Dilated cardiomyopathy (DCM) is a condition where the heart muscle is weakened, leading to an enlargement of the left ventricle. 👉In its advanced stages, DCM often requires interventions such as a durable left ventricular assist device or a heart transplant. 👉While DCM is recognized to have a genetic foundation, the investigation of rare variants in advanced stages of the disease has only recently gained attention. 👉A recent study has demonstrated the effectiveness of genetic testing in advanced DCM cases. Patients experiencing advanced DCM were found to be 2 ½ times more likely to carry a rare variant in a relevant DCM gene compared to those with less severe heart disease. 👉This discovery provides additional insights for healthcare professionals to better assess the risk of outcomes in managing DCM patients and identifying at-risk family members. We at 4bases take pride in offering healthcare providers CARDIO pro, a kit utilizing Next Generation Sequencing Technologies for the genetic profiling of familial cardiovascular diseases. #DCM #genetictesting #CARDIOpro #NGS #4bases Sources: Mark Hofmeyer, Garrie Haas, Jinwen Cao, Evan Kransdorf, Ewald, G. A., Alanna Morris, Anjali Owens, A. T., Brian Lowes, D. Stoller, D., Tang, W. W., Garg, S., Barry Trachtenberg, Salpy Pamboukian, S. V., Nancy Sweitzer, Wheeler, M. T., Wilcox, J. E., Katz, S. D., Hershberger, R. E. (2023b).  Rare variant genetics and dilated cardiomyopathy severity : The DCM Precision Medicine Study. Circulation, 148(11), 872‑881.  https://lnkd.in/eVctyPa9 Study shows benefit of routine genetic testing of dilated cardiomyopathy patients with advanced heart disease.  The Ohio State University Wexner Medical Center.  https://lnkd.in/ecAhAXmn

Gene editing therapy has just been approved for sickle cell disease (SCD) and beta-thalassemia. To understand the potential impact this has, it may be useful to remember how SCD can significantly affect patients' lives, namely children. Though especially focused on the role of oxidative stress on the disease, particularly on vascular brain disease in children, it is a comprehensive review on SCD. It also addresses genetic modulation (variants other than the causal genetic change) as an underlying factor influencing the significant clinical variation between patients. https://lnkd.in/dg9agGEa #SickleCellDisease #SCDreview #OxidativeStress #PediatricStroke #GeneticModulation P.S. #SciRiddles returns tomorrow

Free On-Demand Webinar: Understand Toxin Genetics testing with Dr. Emmie Brown, ND Genetic variations in genes that code for detox enzymes can affect detoxification in the body, leaving patients susceptible to inefficient detoxing, toxic build-ups, or infections. An impaired detoxification system is linked to a wide range of conditions and chronic diseases, including cancer, cardiovascular disease, and neurological conditions like Alzheimer’s disease. In this free on-demand webinar, you'll learn: 🧪 The role of genetic polymorphisms (SNPs) in toxin detoxification 🧫 Insights into liver detox processes, xenobiotics, and genotoxins 📊 Clinical indications for testing and interpreting results 📈 How to use Toxin Genetics testing with the Total Tox Burden and other companion tests effectively 🛠️ Practical applications and monitoring strategies in clinical settings Access the webinar now to optimize your detox and wellness strategies! https://hubs.ly/Q02hrP4t0

📖 A rare malignancy in children 📖 An 18 month old child with history of pale stools from birth and jaundice from third month. USG showed multiple hypoechoic liver lesions with cirrhosis and portal hypertension. CECT was suggestive of multifocal HCC. AFP levels were more than 150000 ng/ml. Genetic panel testing showed ABCB11 mutation. FDG PET/CT images are given. Multiple FDG avid arterial hyperenhacing lesion with portovenous washout are seen, suggesting multifocal HCC with no distant metastases observed. 🚨 Understanding ABCB11 Mutation & Hepatocellular Carcinoma (HCC) 🚨 🔍 Incidence: ABCB11 mutations, linked with rare liver diseases like PFIC2, can increase HCC risk. Incidence is low but significant in PFIC2 patients. 🧬 Pathophysiology: ABCB11 gene encodes bile salt export pump (BSEP), crucial for bile acid transport. Mutations cause bile acid buildup, liver damage, cholestasis, & cirrhosis—risk factors for HCC. ⚠️ Symptoms: Chronic cholestasis, jaundice, pruritus, hepatomegaly, growth retardation. Advanced stages: abdominal pain, weight loss, fatigue, liver failure signs (ascites, variceal bleeding). 🩺 Diagnosis: Genetic testing for ABCB11 mutations. Liver function tests, imaging (ultrasound, CT, MRI), liver biopsy. Monitoring alpha-fetoprotein (AFP) levels. 🛡️ Early detection & regular monitoring can improve outcomes. Stay informed! 🌟 #LiverHealth #Genetics #FDG #Nuclear Medicine #HCC #ABCB11 #MedicalResearch #HealthcareInnovation

The revolutionary gene therapy for sickle cell disease from CRISPR Therapuetics is not without side effects. Scientists are working on better drugs to eliminate, for example, hair loss and mouth sores. Learn more in our cover story. https://lnkd.in/g_gqQUvR

Review by Dr. Takeshi Tokuyama and Prof. Shigeru Yanagi summarizes the role of mitochondrial morphology in heart diseases for each mitochondrial morphology regulatory gene, and their potential as therapeutic targets to heart diseases: https://lnkd.in/dS_cYtuq

Case of the week: 1 year old boy with Hypertrophic cardiomyopathy (#HCM) referred for comprehensive cardio genetic testing. 📌 Results: Pathogenic variant c.390C>G (p.Ile130Met) in #TRIM63 gene was found. A delicate balance between protein synthesis and degradation maintains cardiac size and function. TRIM63 encoding Muscle RING Finger 1 (MuRF1) maintains muscle protein homeostasis by tagging the sarcomere proteins with ubiquitin for subsequent degradation by the ubiquitin-proteasome system (UPS). 📌 Conclusion: Cardiovascular diseases are the leading cause of death throughout the world. Although many causes of the disease can be linked to the lifestyle, inactivity and behavior, there still much more to learn about how genetics can contribute to disease. Recently, the American Heart Association (#AHA) issued a statement recommending genetic testing for patients diagnosed with all forms of #cardiomyopathy. In addition, the American College’s of Cardiology (#ACC) and European Society of Cardiology (#ESC) recommended genetic testing for individuals with a personal or family history of #suddencardiacarrest , or for individuals with a personal or family history of certain inherited #arrhythmias. 🧬🧬🧬 There is a need for comperhensive cardio genetic testing as geno-phenotypes are often overlapping, dozens of genes are responsible for more than 17 inherited cardiovascular disease syndromes. 🧬🧬🧬 Hereditary Cardiovascular disease: 🔷Cardiomyopathies 🔷Cadiac Channelopthies 🔷Aortopathies 🔷Lipid disorders Benefits of early genetic testing: 🔵Detection before any symptoms or fatality occurs. 🔵Significantly reduces diagnostic delay. 🔵Enables to start early treatment to slow down organ damage and prevent an advance disease. 🔵Personalized treatment and reduced overall cost. #cardiovasculardisease #cardiovascularhealth #cardiovascular #genetictesting #inheritance #suddencardiacarrest #ngs #comperhensive #preventivemedicine #personalizedmedicine #Familiar #Hypercholesterolemia #FH

Exciting Breakthrough in IBD Research Employing Human Tissue Assays! A recent discovery by scientists at The Francis Crick Institute and University College London has unveiled a significant genetic factor contributing to inflammatory bowel disease (IBD). This groundbreaking research in functional genomics identifies a weak spot in DNA that affects the behaviour of macrophages, leading to excessive inflammation in the bowels. With Crohn’s disease and ulcerative colitis affecting millions globally, this finding marks a pivotal step towards understanding and potentially curing IBD. At REPROCELL, we are at the forefront of drug discovery, and this research aligns perfectly with our mission, by combining genomics with pharmacology. Our advanced assays, including those specifically for IBD, are designed to identify and develop targeted treatments that address the root causes of diseases. The identification of a key “regulator” gene of inflammation opens new avenues for creating more effective and personalized therapies. Using tests in ex vivo tissues from patients with IBD (as routinely done by REPROCELL), the research team found that certain existing drugs can reverse excessive inflammation, providing a head start toward developing new treatments. However, challenges remain in targeting these treatments precisely to avoid side effects and ensure they do not impair beneficial inflammation. We are excited to see such progress in the field and are committed to contributing to these advancements as we move closer to a world free from the debilitating impacts of IBD. Check out our IBD assay here: https://lnkd.in/eDhPDbUh Read more about the breakthrough in the BBC article: https://lnkd.in/e3QJ3FFb REPROCELL’s paper on functional genomics using human tissue and the use of machine learning in IBD research: https://lnkd.in/daRW7yM9

Why women are more affected by autoimmune diseases is now clarified! The culprit is the gene XIST (technically a non-coding RNA). XIST is in charge of the random suppression of the extra X chromosome, and for such reason, it is only expressed in women. After cell damage, XIST can become the target of autoimmune attacks only in females. This knowledge opens avenues for new therapies for MS, NMO, and other autoimmune diseases. #MS #autoimmunedisease #nmo https://lnkd.in/diyTketA

Human microglial state dynamics in #Alzheimer’s disease progression:- •Altered microglial states affect neuroinflammation, neurodegeneration, and disease but remain poorly understood. •Here, we report 194,000 single-nucleus microglial transcriptomes and epigenomes across 443 human subjects and diverse Alzheimer’s disease (AD) pathological phenotypes. •We annotate 12 microglial transcriptional states, including AD-dysregulated homeostatic, inflammatory, and lipid-processing states. •We identify 1,542 AD-differentially-expressed genes, including both microglia-state-specific and disease-stage-specific alterations. •By integrating epigenomic, transcriptomic, and motif information, we infer upstream regulators of microglial cell states, gene-regulatory networks, enhancer-gene links, and transcription-factor-driven microglial state transitions. •We demonstrate that ectopic expression of our predicted homeostatic-state activators induces homeostatic features in human iPSC-derived microglia-like cells, while inhibiting activators of inflammation can block inflammatory progression. •Lastly, we pinpoint the expression of AD-risk genes in microglial states and differential expression of AD-risk genes and their regulators during AD progression. Overall, we provide insights underlying microglial states, including state-specific and AD-stage-specific microglial alterations at unprecedented resolution. #highlights:- •Single-nucleus transcriptomes and epigenomes of human microglia. •Microglia state-specific and disease-stage-specific profile in Alzheimer’s disease. •Chromatin accessibility poorly captured microglia transcriptional state diversity. •Transcription factor networks regulate microglial states and their transitions.