MOLECULAR CHARACTERIZATION OF FAMILIAL LYMPHEDEMA

描述(改编自研究人员摘要)：原发性淋巴水肿是一种 淋巴引流不足的状况，导致 肿胀，经常复发的蜂窝组织，以及患肢的畸形 或下半身，在没有血管、心脏、外科、肾脏或肝脏的情况下 导致浮肿的原因。 PI绘制了三种不同形式的遗传性原发淋巴水肿 常染色体显性遗传：原发性先天性(PCL)，起病于青春期(POL，The 最常见的)，以及罕见的淋巴水肿-二叉症综合征(LDS) 有淋巴管增生、胸管发育不全或发育不良； 常见心脏畸形，伴有双排睫毛 (二叉虫病)。定位于5q35.3的原发性先天性淋巴水肿是 最近来自芬兰的一组调查人员显示，在一些 家系的胞浆酪氨酸激酶域的错义突变 VEGFR3基因。 这项建议的具体目的有两个：1)研究基因 113个家系与PCL、LDS、POL 3个位点的连锁关系 在本研究过程中可能提供的其他地点，以及 确定每个淋巴水肿基因座对总体的遗传贡献 这种表型的表现；以及2)在一些 POL(和/或PCL)候选基因，并最终识别、克隆、分离和 确定可能的淋巴水肿基因的特征。根据这些结果，他们 可能会开始另一轮全基因组搜索，每隔5厘米按顺序 以确定未知的其他POL基因座的染色体位置。

DESCRIPTION (Adapted from investigator's abstract): Primary lymphedema is a condition in which there is a deficiency of lymphatic drainage, leading to swelling, frequent recurrent cellulites, and disfigurement of the affected limb or lower torso, in the absence of vascular, cardiac, surgical, renal or hepatic causes for the edema. The PI has mapped three different forms of primary lymphedema inherited as autosomal dominants: primary congenital (PCL), onset with puberty (POL, the most common), and the rare lymphedema-distichiasis syndrome (LDS) in which there is hyperplasia of lymphatics, aplasia or hypoplasia of thoracic duct, and frequent cardiac malformations, in association with double row of eyelashes (distichiasis). The primary congenital lymphedema, mapped to 5q35.3, was recently shown by a group of investigators from Finland to be due in some families to missense mutations in the cytoplasmic tyrosine kinase domain of the vegfr3 gene. The specific aims of this proposal are two fold: 1) to investigate the genetic linkage relationship of 113 families to 3 sites of PCL, LDS and POL as well as other locations that may become available during the course of this study and, to determine the genetic contribution of each lymphedema locus to the overall presentation of this phenotype; and 2) to search for mutation in a number of POL (and/or PCL) candidate genes and eventually to identify, clone, isolate and characterize the putative lymphedema genes. Depending on these results, they may embark on another round of a genome-wide search at 5-cM intervals in order to identify the chromosomal location of as yet unknown other POL loci.