MOLECULAR CHARACTERIZATION OF FAMILIAL LYMPHEDEMA

描述（改编自研究者摘要）：原发性脑水肿是一种 一种淋巴引流不足的状况，导致 肿胀、经常复发的蜂窝织炎和患肢的畸形 或下躯干，在没有血管、心脏、外科、肾脏或肝脏的情况下 水肿的原因。 PI绘制了三种不同形式的原发性水肿遗传， 常染色体显性遗传：原发性先天性（PCL），青春期发病（POL， 最常见），以及罕见的水肿-双歧综合征（LDS），其中 存在胸导管增生、发育不全或发育不全，以及 频繁的心脏畸形，与双排睫毛相关 （双睾吸虫病）。原发性先天性水肿，定位于5q35.3， 芬兰的一组调查人员最近显示， 家族错义突变的细胞质酪氨酸激酶结构域的 vegfr 3基因。 这项建议的具体目标有两个方面：1）研究遗传学， 113个家系与PCL、LDS和POL 3个位点的连锁关系， 本研究期间可能提供的其他地点， 以确定每个水肿基因座对总体水肿的遗传贡献， 这种表型的呈现;和2）在许多 POL（和/或PCL）候选基因，并最终鉴定、克隆、分离和 表征推定的水肿基因。根据这些结果，他们 可能会以5厘米的间隔进行另一轮全基因组搜索， 以确定其他未知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.