GENETIC ANALYSIS OF LIMB MALFORMATION DISORDERS

点击翻译按钮获取中文摘要

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.