A5046179146- Congenital Heart Disease Studies
- Congenital heart defects research
- Cardiomyopathy and Myosin Studies
- Genomics and Rare Diseases
- Cardiac Valve Diseases and Treatments
- BRCA gene mutations in cancer
- Genomic variations and chromosomal abnormalities
- Cardiovascular Issues in Pregnancy
- Prenatal Screening and Diagnostics
- Cardiac Arrhythmias and Treatments
- Ethics in Clinical Research
- Cardiac electrophysiology and arrhythmias
- Cardiac pacing and defibrillation studies
- Genetic factors in colorectal cancer
- Cardiovascular Effects of Exercise
- Coronary Artery Anomalies
- Aortic Disease and Treatment Approaches
- Cancer Genomics and Diagnostics
- Protein Tyrosine Phosphatases
- Connective tissue disorders research
- Mobile Health and mHealth Applications
- Williams Syndrome Research
- CRISPR and Genetic Engineering
- Galectins and Cancer Biology
- Developmental Biology and Gene Regulation
Baylor College of Medicine
2023
American College of Medical Genetics
2023
Indiana University School of Medicine
2019-2023
Indiana University – Purdue University Indianapolis
2019-2023
Nationwide Children's Hospital
2008-2022
The Ohio State University
2009-2022
National Society of Genetic Counselors
2019
Mercy Fitzgerald Hospital
2015
There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into best practices in the areas of sequence data generation, analysis, interpretation reporting. The CLARITY Challenge was designed spur convergence diagnosing genetic disease starting from case history data. DNA samples were obtained three families with heritable disorders genomic donated by platform vendors....
Congenital aortic valve stenosis (AVS), coarctation of the aorta (COA) and hypoplastic left heart syndrome (HLHS) are congenital cardiovascular malformations that all involve ventricular outflow tract (LVOT). They presumably caused by a similar developmental mechanism involving developing endothelium. The exact etiology for most LVOT is unknown, but strong genetic component has been established. We demonstrate here mutations in gene NOTCH1 , coding receptor developmentally important...
Congenital heart disease (CHD) is the most common type of birth defect with family- and population-based studies supporting a strong genetic cause for CHD. The goal this study was to determine whether whole exome sequencing (WES) approach could identify pathogenic-segregating variants in multiplex CHD families.WES performed on 9 kindreds familial CHD, 4 atrial septal defects, 2 patent ductus arteriosus, tetralogy Fallot, 1 pulmonary valve dysplasia. Rare (<1% minor allele frequency) that...
Bicuspid aortic valve (BAV) is the most common type of congenital heart disease with a population prevalence 1-2%. While BAV known to be highly heritable, mutations in single genes (such as GATA5 and NOTCH1) have been reported few human cases. Traditional gene sequencing methods are time labor intensive, while next-generation high throughput remains costly for large patient cohorts requires extensive bioinformatics processing. Here we describe an approach targeted multi-gene combinatorial...
Basic knowledge of genetics is essential for understanding genetic testing and counseling. The lack a written, English language, validated, published measure has limited our ability to evaluate patients families. Here, we begin the psychometric analysis true/false measure. 18-item was completed by parents children with congenital heart defects (CHD) (n = 465) adolescents young adults CHD (age: 15-25, n 196) mean total correct score 12.6 [standard deviation (SD) 3.5, range: 0-18]. Utilizing...
Dilated cardiomyopathy ( DCM ) is a disease of the myocardium characterized by left ventricular dilatation and diminished contractile function. Here we describe novel mutation in myosin regulatory light chain RLC ), which aspartic acid at position 94 replaced alanine (D94A). The was identified exome sequencing three adult first‐degree relatives who met formal criteria for idiopathic . To obtain insight into functional significance this pathogenic MYL 2 variant, cloned purified human...
Abstract BACKGROUND The left ventricular outflow tract (LVOT) defects aortic valve stenosis (AVS), coarctation of the aorta (COA), and hypoplastic heart syndrome (HLHS) represent an embryologically related group congenital cardiovascular malformations. They are common cause substantial morbidity mortality. Prior evidence suggests a strong genetic component in their causation. METHODS We selected NRG1 , ERBB3 ERBB4 epidermal growth factor receptor (EGFR) signaling pathway as candidate genes...
Congenital heart defects involving left-sided lesions (LSLs) are relatively common birth with substantial morbidity and mortality. Previous studies have suggested a high heritability complex genetic architecture, such that only few LSL loci been identified. We performed genome-wide case–control association study to address the role of variants using discovery cohort 778 cases 2756 controls. identified significant mapping 200 kb region on chromosome 20q11 [P= 1.72 × 10−8 for rs3746446;...
Congenital heart disease (CHD) is a common group of birth defects with strong genetic contribution to their etiology, but historically the diagnostic yield from exome studies isolated CHD has been low. Pleiotropy, variable expressivity, and difficulty accurately phenotyping newborns contribute this problem. We hypothesized that performing sequencing on selected individuals in families multiple members affected by left-sided CHD, then filtering variants population frequency, silico predictive...
PurposeFor patients with congenital heart disease (CHD), the most common birth defect, genetic evaluation is not universally accepted, and current practices are anecdotal. Here, we analyzed across centers, determined diagnostic yield of testing, identified phenotypic features associated abnormal results.MethodsThis a multicenter cross-sectional study 5 large children's hospitals, including 2899 children ≤14 months undergoing surgical repair for CHD from 2013 to 2016, followed by multivariate...
Congenital heart disease (CHD) is an indication which spans multiple specialties across various genetic counseling practices. This practice resource aims to provide guidance on key considerations when approaching for this particular while recognizing the rapidly changing landscape of knowledge within domain. was developed with consensus from a diverse group certified counselors utilizing literature relevant CHD and aimed at supporting who encounter in their both pre- postnatally.
Hypertrophic cardiomyopathy (HCM) is characterized by thickening of the ventricular muscle without dilation and often associated with dominant pathogenic variants in cardiac sarcomeric protein genes. Here, we report a family two infants diagnosed infantile-onset HCM mitral valve dysplasia that led to death before one year age. Using exome sequencing, discovered affected children had homozygous frameshift variant Myosin light chain 2 (MYL2:NM_000432.3:c.431_432delCT:...
Clinical genetic testing for specific isolated congenital heart defects (CHD) is becoming standard of care in pediatric cardiology practice. Both knowledge and attitudes toward are associated with an increased utilization testing, but these factors have not been evaluated parents children CHD. We mailed a survey to measure the demographics, knowledge, towards CHD who previously consented participate separate research study etiology left ventricular outflow tract malformations (LVOT). Of 378...
Congenital left‐sided cardiac lesions (LSLs) are a significant contributor to the mortality and morbidity of congenital heart disease (CHD). Structural copy number variants (CNVs) have been implicated in LSL without extra‐cardiac features; however, non‐penetrance variable expressivity created uncertainty over use CNV analyses such patients. High‐density SNP microarray genotyping data were used infer large, likely‐pathogenic, autosomal CNVs cohort 1,139 probands with their families....
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...