CARDIAC GENETICS REGISTRY FOR CONGENITAL CARDIOVASCULAR DISEASE

先天性心血管疾病心脏遗传学登记

• 批准号: 7607238
• 负责人: LESLIE B SMOOT
• 金额: $ 0.14万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7607238
• 关键词: Affect; Aortic Valve Stenosis; Cardiac; Cardiovascular Abnormalities; Chromosome Deletion; Chromosomes, Human, Pair 22; Chromosomes, Human, Pair 7; Complex; Computer Retrieval of Information on Scientific Projects Database; Condition; Congenital Heart Defects; Cytogenetics; Diagnostic; Disease; Disruption; Dominant Genetic Conditions; Elastin; Etiology; Family; Funding; Genes; Genetic; Grant; Hereditary Disease; Individual; Institution; Lead; Link; Literature; Modeling; Molecular; Mutation; Numbers; Outcome; Pathway interactions; Point Mutation; Proteins; Research; Research Personnel; Resources; Risk; Screening procedure; Shprintzen syndrome; Source; Syndrome; Testing; United States National Institutes of Health; Vascular Diseases; Williams Syndrome; genetic registry; microdeletion

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Current literature suggests that while etiologies remain complex, a number of congenital cardiac malformations can be linked to specific heritable factors. A broad multi-factorial model is gradually being replaced with disease specific models where independent genetic and/or teratogenic pathways may lead to a particular outcome. These genetic pathways include chromosome deletions, disruptions (translocations), duplications of particular genetic regions, point mutations involving single genes, or alterations in the ability for a gene to be transcribed into a functional protein. In recent years, researchers have identified associations between a number of cardiac syndromes and diagnostic molecular findings. Examples include identification of microdeletions of chromosome 7 (Williams syndrome) and chromosome 22 (Velo-cardio-facial syndrome) both of which clinically manifest cardiac and non-cardiac findings. Commercial cytogenetic probes have recently become available for these two genetic disorders, enabling standardized testing. Individuals with Williams syndrome have haploinsuffficiency for multiple genes. Additionally there are individuals and families with isolated vascular disease (supravalvar aortic stenosis) caused by mutations involving a single gene within the Williams syndrome region. Individuals with "Williams-like" vascular disease may pass on this condition as a dominant trait, although this condition is currently detectable only by using specific screening for elastin mutations. These individuals will show no abnormality using commercial cytogenetic testing for Williams syndrome, yet possess a significant risk of bearing offspring affected with vascular disease.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 目前的文献表明，虽然病因仍然复杂，但许多先天性心脏畸形可能与特定的遗传因素有关。 广泛的多因素模型逐渐被疾病特异性模型所取代，其中独立的遗传和/或致畸途径可能导致特定的结果。 这些遗传途径包括染色体缺失、破坏（易位）、特定遗传区域的重复、涉及单个基因的点突变或基因转录成功能蛋白的能力的改变。 近年来，研究人员已经确定了许多心脏综合征与诊断分子发现之间的关联。 例子包括识别 7 号染色体（威廉姆斯综合征）和 22 号染色体（Velo-cardio-facial 综合征）的微缺失，这两种染色体都在临床上表现出心脏和非心脏的症状。 商业细胞遗传学探针最近已可用于这两种遗传性疾病，从而实现标准化测试。 患有威廉姆斯综合征的个体存在多个基因的单倍体不足。 此外，还有一些个人和家庭患有孤立性血管疾病（瓣上主动脉瓣狭窄），这些疾病是由威廉姆斯综合征区域内的单个基因突变引起的。 患有“威廉姆斯样”血管疾病的个体可能会将这种情况作为显性特征遗传，尽管目前这种情况只能通过对弹性蛋白突变进行特异性筛查来检测。 这些人使用威廉姆斯综合征的商业细胞遗传学检测不会显示出异常，但具有生育患有血管疾病的后代的显着风险。