Congenital Heart Disease Expert Curation Panel

先天性心脏病专家治疗小组

基本信息

批准号：
10413445
负责人：
BRUCE D GELB
金额：
$ 41.34万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10413445
关键词：
Address Affect Animal Model Attention Benign Biological Assay Birth Boston Candidate Disease Gene Cardiac Cardiac development Cardiovascular Diseases Cardiovascular system Cells Classification ClinVar Clinical Collaborations Communication Communities Complex Congenital Abnormality Congenital Heart Defects Data Development Diagnosis Diagnostic Disease Epidemiology Funding Genes Genetic Genetic Research Genetic Variation Genome Genotype Goals Heart Abnormalities Heritability Human Genetics Individual Infant Institutes Intellectual functioning disability International Laboratories Medical Genetics Mentors Modeling Mutation Newborn Infant Outcome Participant Pathogenesis Pathogenicity Patients Pediatric Cardiac Genomics Consortium Phenotype Procedures Research Review Literature Risk Role Science Single Nucleotide Polymorphism Structural defect Syndrome Testing Training United States National Institutes of Health Variant Work autism spectrum disorder base bicuspid aortic valve biochemical model cardiogenesis clinical care clinically relevant clinically significant comorbidity congenital heart disorder exome sequencing experience genetic architecture genetic panel test genetic testing genetic variant genome-wide insertion/deletion mutation interest member next generation sequencing novel outreach research clinical testing trait

项目摘要

ClinGen CHD ECP Project Summary Abstract Congenital heart defects (CHD), defined as structural malformations of the heart and great vessels that are present at birth, are the commonest birth defects, affecting 2-3% of newborns when bicuspid aortic valve is included. While understood to be potentially a heritable trait as early as the mid-1800s, definitive epidemiological evidence supporting the notion that CHD was primarily genetic in its origins has only emerged in the last 35 years. To date, 253 genes contributing to CHD have been established but a far smaller number of genes have been designated as CHD-causing using formal ClinGen gene curation. Furthermore, and there are clinically relevant discrepancies for individual variants (i.e., pathogenic/likely pathogenic vs. benign/likely benign) in a substantial number of these genes. Sequencing-based clinical genetic testing using CHD gene panels facilitates diagnoses for which there are actionable co-morbidities that would often go otherwise undetected, particularly in young infants in whom syndromic features may not yet be evident but available commercial CHD genetic testing panels vary substantially in their gene content. The proposed CHD ECP will bring together experts in CHD genes from around the world which, in a well-organized, ClinGen-compliant manner, will curate gene-CHD pairs and classify their variants. The MPI's and many of the Expert Curation Panel members have extensive prior collaboration on a long-standing NIH-supported consortium (Pediatric Cardiac Genomic Consortium) that has and continues to elucidate the genetic architecture of the trait of interest (CHD) thus bringing significant gene and variant curation experience. An emphasis will be placed on developing experimental evidence criteria for a given CHD trait, drawing from a notably broad range of science (biochemical, cell-based, and animal models of heart development). This effort is well timed as the numbers of potential genes available for clinical genetic testing is rising rapidly and the clinical utility of such testing is well established. Further, candidate CHD genes with compelling human genetic evidence for pathogenicity but scant functional data can be shared with the cardiac developmental research community for consideration. The CHD ECP will fill an important gap in clinical care.

Clingen CHD ECP项目摘要摘要先天性心脏缺陷（CHD），被定义为心脏的结构畸形和伟大的血管出生时存在，是最常见的先天缺陷，当双刺主动脉瓣为2-3％的新生儿包括。虽然最早在1800年代中期就被认为是一种可遗传的特征流行病学证据支持CHD主要是其起源遗传的观念在过去的35年中。迄今为止，已经建立了253个为CHD造成的基因，但数量少得多使用正式的克林根基因策展指定为引起CHD的基因。此外，还有单个变异的临床相关差异（即致病/可能的致病性与良性/可能良性）在这些基因的大量基因中。基于测序的临床基因检测使用冠心病基因面板促进了有可行的合并症通常会发生的诊断未被发现，尤其是在综合症特征可能尚不明显但可用的年轻婴儿中商业CHD遗传测试面板的基因含量差异很大。拟议的CHD ECP将将来自世界各地的CHD基因的专家汇聚在一起，这些专家在一个符合凝结的良好，符合凝结的人中方式将策划基因-CHD对并分类它们的变体。 MPI和许多专家策划小组成员在长期存在的NIH支持财团（小儿具有并继续阐明的心脏基因组财团）兴趣（CHD），从而带来了重要的基因和变异的策展经验。将重点放在为给定的CHD特征开发实验证据标准，源于广泛的科学范围（生化，基于细胞的心脏发育模型）。这项努力的时机是可用于临床基因检测的潜在基因正在迅速上升，这种测试的临床实用性很好已确立的。此外，具有诱人人类遗传学证据的候选冠心病基因，但可以与心脏发展研究社区共享功能数据很少，以供考虑。这 CHD ECP将填补临床护理中的重要空白。