CARDIAC GENETICS REGISTRY FOR CONGENITAL CARDIOVASCULAR DISEASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目前的文献表明，虽然病因仍然复杂，但一些先天性心脏畸形可能与特定的遗传因素有关。一个广泛的多因素模型正逐渐被疾病特异性模型所取代，在这些模型中，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删除、破坏(易位)、特定遗传区域的复制、涉及单基因的点突变或基因转录成功能蛋白质的能力的改变。 近年来，研究人员已经确定了一些心脏综合征与诊断分子结果之间的联系。例如7号染色体微缺失(威廉姆斯综合征)和22号染色体微缺失(血管-心脏-面部综合征)，这两种染色体在临床上都表现为心脏和非心脏的表现。商业细胞遗传学探针最近已可用于这两种遗传疾病，使标准化测试成为可能。 威廉姆斯综合征患者存在多个基因的单倍性不足。此外，还有一些个人和家庭患有孤立的血管疾病(瓣膜上动脉狭窄)，这些疾病是由威廉姆斯综合征区域内涉及单一基因的突变引起的。患有“威廉姆斯样”血管疾病的人可能会将这种情况作为显性特征传递给人们，尽管目前这种情况只能通过对弹性蛋白突变的特定筛查来检测。使用威廉姆斯综合征的商业细胞遗传学测试，这些个体不会显示异常，但具有生育受血管疾病影响的后代的重大风险。

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.