ClinGen Expert Curation Panel for Severe Structural Anomalies and Stillbirth

ClinGen 严重结构异常和死产专家管理小组

基本信息

批准号：
10687993
负责人：
RONALD WAPNER
金额：
$ 34.87万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10687993
关键词：
Amniocentesis Area Caring Childhood ClinVar Clinical Clinical Management Complex Congenital Abnormality Consensus Counseling Data Developmental Biology Diagnosis Diagnostic Discipline of obstetrics Disease Edema Etiology Evaluation Fetal Diseases Genes Genetic Genetic Counseling Genomics Genotype Gestational Age Guidelines Hydrops Fetalis Image Individual Infant Infrastructure Institution International Karyotype Laboratories Literature Maternal-fetal medicine Medical Genetics Medicine Molecular Morbidity - disease rate National Institute of Child Health and Human Development Pathogenicity Perinatal Phenotype Policies Pregnancy Pregnancy Outcome Procedures Prognosis Provider Public Domains Recurrence Risk Standardization Structural defect Structure Testing Therapeutic Intervention Ultrasonography Utilization Review Validation Variant Visualization anatomic imaging causal variant clinical care clinical diagnosis clinical imaging clinical practice clinically relevant computer science congenital anomaly developmental disease exome experience fetal genetic variant genome sequencing genomic data improved in utero interest knowledge base member mortality obstetric care prenatal public database reproductive outcome response stillbirth tool

项目摘要

Congenital anomalies occur in approximately 3% of all pregnancies and are a leading cause of perinatal, infant, and childhood mortality and morbidity. The majority of these anomalies are identified during pregnancy but despite the introduction of increasingly more sophisticated prenatal genomic testing such as sequencing, a specific diagnosis is hampered by our inability to accurately interpret genomic data. A leading barrier to interpretation is the lack of expert consensus regarding gene-disease association, variant pathogenicity, and actionability of findings, creating challenges for obstetric and genetic providers to offer appropriate care. Accordingly, in response to the Eunice Kennedy Shriver National institute of Child Health and Human Development's interest in the genomics of birth defects, this application is a proposal to become a participating ClinGen expert panel to evaluate the clinical relevance of genes and variants related to fetal congenital anomalies. Our proposal will develop gene disease validity and variant curation expert panels to evaluate two common and unique severe fetal disorders: non-immune fetal hydrops and unexplained stillbirth. The variant and gene curation panels are composed of experts in clinical genetics, maternal fetal medicine, molecular laboratory testing, computer science, developmental biology, genetic counseling and biocuration. Members of our expert panel come from diverse national and international institutions and have extensive experience in prenatal phenotyping and genotyping. The panel also has members who have served on other ClinGen expert panels and committees, which will facilitate our integration into the ClinGen infrastructure. Our proposal describes the details of our intended use of ClinGen policies, procedures, and tools to best determine the clinical relevance of specific genes and variants to clinical care. We are committed to sharing our data and results with others and contributing to the genetic knowledge base in the area of early developmental disease.

先天性异常发生在大约 3% 的妊娠中，是围产期、婴儿、以及儿童死亡率和发病率。这些异常大多数是在怀孕期间发现的，但尽管引入了越来越复杂的产前基因组测试（例如测序），由于我们无法准确解释基因组数据，具体诊断受到阻碍。的主要障碍解释是缺乏关于基因与疾病关联、变异致病性和研究结果的可操作性，给产科和遗传提供者提供适当的护理带来了挑战。因此，针对尤尼斯·肯尼迪·施赖弗国家儿童健康与人类研究所的回应发展对出生缺陷基因组学的兴趣，此应用程序是成为参与的提案 ClinGen 专家小组评估与胎儿先天性相关的基因和变异的临床相关性异常。我们的提案将开发基因疾病有效性和变异管理专家小组来评估两个常见和独特的严重胎儿疾病：非免疫性胎儿水肿和不明原因的死产。变异和基因管理小组由临床遗传学、母胎医学、分子实验室测试、计算机科学、发育生物学、遗传咨询和生物管理。我们的专家小组成员来自不同的国家和国际机构，拥有广泛的经验具有产前表型和基因分型的经验。该小组还有曾在其他机构任职的成员 ClinGen 专家小组和委员会，这将有助于我们融入 ClinGen 基础设施。我们的提案描述了我们打算使用 ClinGen 政策、程序和工具的详细信息，以实现最佳效果确定特定基因和变异与临床护理的临床相关性。我们致力于分享我们的与他人合作的数据和结果，为早期发育领域的遗传知识库做出贡献疾病。