中文摘要：

目的 对1个患原发性先天性淋巴水肿（prjmary congenital lymphoedema,PCL）汉族大家系进行遗传学研究,了解先天性淋巴水肿患病的分子遗传学基础.方法 对该家系12名成员（10名直系亲属、2名配偶）采样并提取DNA,选择已知的3个PCL相关致病基因位点,用荧光微卫星标记进行基因连锁定位.确定VEGFR3为致病基因后,对家系中的患者进行VEGFR3基因的突变检测,并与100名正常人进行对照分析.结果 该家系疾病与5q35.3区的微卫星标记D5S408连锁.对该区域的VEGFR3进行DNA测序,发现患者含有1个c.C3341T转换,该突变导致VEGFR3蛋白发生p.Pro1114Leu;该家系中所检测患者均发现携带该杂合突变.100名正常对照该位点的测序分析未能检测到该突变.结论 VEGFR3基因是最重要的PCL致病基因,该家系成员VEGFR-3的p.Pro1114Leu突变是患者患淋巴水肿的遗传基础.

英文摘要：

Objective To identify the disease-causing gene in a four-generation Chinese family with 9 members affected with primary congenital lymphoedema （PCL, also known as Milroy disease）. Methods Linkage analysis was performed with a few microsatellite markers flanking the candidate genetic loci for PCL, including 3 known genes associated with autosomal dominant PCL. For mutation analysis, VEGFR3 gene was sequenced with DNA from the proband. Direct DNA sequencing of exon 25 of the VEGFR3 gene was performed in all family members. Results The disease gene in the family was mapped to chromosome 5q35. 3 with a maximum Lod score of 2. 07. Direct DNA sequencing of VEGFR3 gene revealed a heterozygous C to T transition at nucleotide 3341, resulting in p. Pro1114Leu mutation. The p. Pro1114Leu mutation co-segregated with all affected individuals in the family. Conclusion This study identified a C3341T （p. Pro1114Leu） mutation in the VEGFR3 gene in a Chinese family with PCL, provided evidence that VEGFR3 mutation can cause PCL in Chinese.