A5014073885- Cardiomyopathy and Myosin Studies
- Cardiac electrophysiology and arrhythmias
- BRCA gene mutations in cancer
- Cardiac pacing and defibrillation studies
- Genomics and Rare Diseases
- Congenital heart defects research
- Cardiac Arrhythmias and Treatments
- RNA Research and Splicing
- Ion channel regulation and function
- Erythrocyte Function and Pathophysiology
- RNA and protein synthesis mechanisms
- Cardiovascular Effects of Exercise
- Cardiovascular Issues in Pregnancy
- Connective tissue disorders research
- Nuclear Structure and Function
- Tracheal and airway disorders
- Congenital Ear and Nasal Anomalies
- Genetic Associations and Epidemiology
- Ion Transport and Channel Regulation
- Mitochondrial Function and Pathology
- Congenital Heart Disease Studies
- Genetic Neurodegenerative Diseases
- Genetic factors in colorectal cancer
- Ethics in Clinical Research
- Genomic variations and chromosomal abnormalities
Indiana University – Purdue University Indianapolis
2013-2022
Indiana University School of Medicine
2013-2022
Riley Hospital for Children
2017
Indiana University Health
2017
Indiana University
2016
Indiana University Bloomington
2016
University of Indianapolis
2015
The Ohio State University Wexner Medical Center
2015
The Ohio State University
2015
Hong Kong University of Science and Technology
2015
PurposeIntegrating genomic sequencing in clinical care requires standardization of variant interpretation practices. The Clinical Genome Resource has established expert panels to adapt the American College Medical Genetics and Genomics/Association for Molecular Pathology classification framework specific genes diseases. Cardiomyopathy Expert Panel selected MYH7, a key contributor inherited cardiomyopathies, as pilot gene develop broadly applicable approach.MethodsExpert revisions were tested...
Background— The cardiac cytoskeleton plays key roles in maintaining myocyte structural integrity health and disease. In fact, human mutations cytoskeletal elements are tightly linked to pathologies, including myopathies, aortopathies, dystrophies. Conversely, the link between protein dysfunction electric activity is not well understood often overlooked arrhythmia field. Methods Results— Here, we uncover a new mechanism for regulation of membrane excitability. We report that βII spectrin, an...
Abstract RBM20 is a major regulator of heart-specific alternative pre-mRNA splicing TTN encoding giant sarcomeric protein titin. Mutation in linked to autosomal-dominant familial dilated cardiomyopathy (DCM), yet most the missense mutations and sporadic cases were mapped an RSRSP stretch arginine/serine-rich region which function remains unknown. In present study, we identified R634W mutation within G1031X nonsense cohorts DCM patients. We demonstrate that two serine residues are...
Abstract Cardiovascular genetic counseling (CVGC) is recommended for a variety of inherited heart conditions; however, its impact on patient empowerment has not been assessed. The Genetic Counseling Outcome Scale (GCOS) validated reported outcome tool which measures to capture the clinical genetics services. As routine practice at our center, adult patients attending CVGC appointment complete 24‐item GCOS survey and 5‐item knowledge cardiac surveillance recommendations relatives prior clinic...
Abstract We sought to delineate the genetic test review and interpretation practices of clinical cardiovascular counselors. A one‐time anonymous online survey was taken by 46 counselors recruited through National Society Genetic Counselors Cardiovascular Special Interest Group. Nearly all (95.7%) gather additional information on variants reported reports most (81.4%) assess classification such variants. Clinical typically (81.0%) classify in collaboration with cardiologist and/or geneticist...
Inherited cardiovascular conditions are common, and comprehensive care of affected families often involves genetic testing. When the clinical presentations these overlap, testing may clarify diagnoses, etiologies, treatments in symptomatic individuals facilitate identification asymptomatic, at-risk relatives, allowing for life-saving preventative care. Although some professional society guidelines on inherited cardiac include recommendations, they quickly become outdated owing to rapid...
We performed whole exome sequencing in individuals from a family with autosomal dominant gastropathy resembling Ménétrier disease, premalignant gastric disorder epithelial hyperplasia and enhanced EGFR signalling. disease is believed to be an acquired disorder, but its aetiology unknown. In affected members, we found missense p.V742G variant MIB2, gene regulating NOTCH signalling that has not been previously linked human diseases. The segregated the pedigree, highly conserved amino acid...
The development of high throughput technologies such as next generation sequencing (NGS) has allowed for thousands DNA loci to be interrogated simultaneously in a fast and economical method the detection clinically deleterious variants. Whenever clinical diagnosis is known, targeted NGS approach involving use disease-specific gene panels can employed. This often valuable it allows more specific relevant interpretation results. Here we describe customization, validation, utilization...
Abstract Cardiovascular genetic counseling has expanded as an established specialty over the last 20 years. Despite guidelines recommending for heritable cardiac diseases, there have been limited descriptions of practice model types used different clinical indications seen in this subspecialty. We aimed to describe current models by cardiovascular counselors and document strengths, challenges, areas improvement. Genetic counselor respondents ( n = 63) who self‐reported seeing were recruited...
For the past two decades, guidelines put forth by American College of Medical Genetics and Genomics (ACMG) detailing providers' clinical responsibility to recontact patients have remained mostly unchanged, despite evolving variant interpretation practices which yielded substantial rates reclassification amended reports. In fact, there is little information regarding genetic counselors' roles in informing reclassified variants, or process these reports are currently being handled. this study,...
Abstract Haploinsufficiency of CHD7 (OMIM# 608892) is known to cause CHARGE syndrome 214800). Molecular testing supports a definitive diagnosis in approximately 65–70% cases. Most mutations arise de novo, and no affecting exon‐7 have been reported date. We report on an 8‐year‐old girl diagnosed with that was referred our laboratory for comprehensive gene screening. Genomic DNA from the subject suspected isolated peripheral blood lymphocytes Sanger sequencing, along deletion/duplication...
Variants in the LMNA gene, which encodes Lamin-A/C, have been commonly associated with cardiac conduction system diseases usually accompanying cardiomyopathy. We seen two unrelated patients who presented atrioventricular block (AVB) or without Genetic testing identified missense variant c.1634G>A (p.R545H) and single nucleotide deletion c.859delG (p.A287Lfs*193). The leads to a shift reading frame subsequent protein truncation. Since impaired Nav1.5 function has reported cause AVB, we...
Introduction: Deleterious variants in the LMNA gene, which encodes for Lamin-A/C, have been shown to be associated with cardiac conduction diseases (CCDs) and cardiomyopathy. We previously reported that two found patients presenting CCDs can prevent -mediated activation of peak sodium current (I Na ). In addition, western blot analyses showed phosphorylation Lamin at serine 22 (S22) was reduced HEK293 cells expressing either variant. Thus, we sought investigate what potential role S22 plays...
We report on the process of post mortem evaluation and genetic testing following death a 25-year-old man due to ascending aortic dissection leading rupture. Following negative clinical 12- gene thoracic aneurysm panel, research revealed novel c.5732A>T (p.E1911V) variant in exon 34 MYLK (NM_053025). Two likely pathogenic variants this have been reported previously individuals with familial dissection. Given unclear consequence found our proband, we classified change as uncertain...