GENETIC ANALYSIS OF LIMB MALFORMATION DISORDERS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该项目的总体目标是研究畸形的病因和发病机制（即，出生缺陷），集中于肢体图案的异常，例如肢体缺陷/重复和多个先天性挛缩（即，关节弯曲）。 具体的研究策略是确定影响肢体畸形风险的基因变异，特别是导致孟德尔肢体畸形疾病的基因变异，随后汇编和分析这些患者及其家属的临床发现，以探讨特定基因突变（即，基因型）和临床特征（即，表型）。 从每名参与者收集的数据将包括相关的临床信息和生物材料（例如，血液、DNA等）。 在研究期间，这些数据将保存在Bamshad博士的实验室。 一旦收集到这些数据，积极参与往往就完成了。 然而，随着对病因学和发病机制的了解的增加，有时需要重新联系参与者以收集更多的表型信息和/或生物材料。 事实上，这种纵向数据的收集往往是非常有价值的了解肢体畸形疾病的自然史，往往是最感兴趣的参与者，部分原因是因为许多肢体畸形疾病的自然史了解甚少，限制了临床决策的证据往往是基于。 我们预计在未来5年内收集约2000人的数据。

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 overall goal of this project is to investigate the etiology and pathogenesis of malformations (i.e., birth defects) of the limb, concentrating on abnormalities of limb patterning such as limb deficiency/duplications and multiple congenital contractures (i.e., arthrogryposis). The specific research strategy is to identify gene variants that influence risk for limb malformations, especially gene variants causing Mendelian limb malformation disorders, and subsequently compile and analyze the clinical findings in these patients and their families in order to explore the relationship between specific gene mutations (i.e., genotype) and clinical characteristics (i.e., phenotype). Data to be collected from each participant will include pertinent clinical information and biological materials (e.g., blood, DNA, etc.). These data will be banked in Dr. Bamshad's lab for the duration of the study. Active participation will often be complete once these data are collected. However, it will sometimes be necessary to re-contact participants to collect further phenotypic information and/or biological materials as knowledge about etiology and pathogenesis increase. Indeed, the collection of such longitudinal data is often of great value in understanding the natural history of limb malformation disorders and often what is of most interest to participants in part because the natural history of many limb malformation disorders is poorly understood limiting the evidence on which clinical decisions are often based. We expect to collect data from ~2000 individuals over the next 5 years.