MOLECULAR GENETICS OF THE OCULO-AURICULO-VERTEBRAL (OAV) SPECTRUM

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。眼-耳-椎（OAV）谱系障碍包括一种独特的出生缺陷模式，涉及眼睛、耳朵和脊柱。目前，大多数OAV病例被认为是非遗传性的（可能是血管或致畸源性的），通常引用的复发风险为2-3%。然而，也有多患病个体的家庭具有常染色体显性遗传模式。在过去的两年里，贝克博士收集了15个这样的家庭的临床信息，主要来自斯坦福医学遗传学服务。虽然我们已经研究了这些患者的临床特征，并提出了一个关于可能区分非遗传性和家族性（可能是遗传性）病例的特征的假设，但最确定的测试将是发现与特定家庭的疾病相关的遗传变化。目前，没有已知的OAV基因，我们建议寻找OAV谱系障碍的遗传原因。在获得IRB批准后，我们将收集可用家族的血液样本进行DNA分离和淋巴细胞转化。我们将进行全基因组连锁研究，以确定包含候选基因的区域。在未来，我们希望从显示显著连锁的区域分离出OAV的基因

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. The oculo-auriculo-vertebral (OAV) spectrum disorder consists of a distinct pattern of birth defects involving eyes, ears, and spine. Currently, most cases of OAV are thought to be non-genetic (possibly of vascular or teratogenic origin), and a recurrence risk of 2-3% is generally quoted. However, there are families of multiple affected individuals with an autosomal dominant mode of inheritance. Over the last two years, Dr. Beck has collected clinical information on 15 such families, predominantly from the Stanford Medical Genetics service. Although we have studied clinical characteristics of these patients and proposed a hypothesis regarding features which might separate non-genetic from familial (likely genetic) cases, the most definitive test would be to discover a genetic change associated with the condition in a specific family. Currently, no genes for OAV are known, and we propose to search for the inherited cause(s) of the OAV spectrum disorder. With IRB approval already obtained, we will collect blood samples from available families for DNA isolation and lymphoblast transformation. We will perform whole genome linkage studies to identify regions containing candidate genes. In the future, we hope to isolate genes responsible for OAV from regions that show significant linkage