A novel VEGFR3 mutation causes Milroy disease
A novel VEGFR3 mutation causes Milroy disease
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DOI：
10.1002/ajmg.a.31703
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发表时间：
2007-06-01
影响因子：
2
通讯作者：
Glover, Thomas W.
中科院分区：
文献类型：
--
作者：
Butler, Matthew G.;Dagenais, Susan L.;Glover, Thomas W.
米尔罗伊病，也称为原发性先天性水肿，是一种常染色体显性遗传的遗传性水肿。患有米尔罗伊病的个体的典型特征是由于淋巴管发育不全引起的下肢水肿的先天性发作。大多数Milroy病病例的遗传基础尚未确定，尽管血管内皮生长因子受体VIEGFR 3（FLT-4）的突变是迄今为止描述的17种突变的一些病例的原因。在这份报告中，我们描述了一个四代遗传家族中一个新VEGFK 3外显子22突变，该家族中先天性水肿以常染色体显性方式分离。除水肿外，受影响的家族成员还具有与Milroy病相关的其他临床表现，包括鞘膜积液、滑跳状脚趾甲、大口径静脉和皮下增厚。我们筛选了VEGFR 3的突变，这些突变揭示了外显子22中的新的3059 A> T颠换，导致VEGFR 3的第二酪氨酸激酶结构域中的Q1020 L错义突变。该突变等位基因在不完全遗传的受影响个体中与水肿分离。这是第一次报告的外显子22突变的米尔罗伊病。(c)2007 Wiley-Liss，Inc.
Milroy disease, also known as primary congenital lymphedema, is a hereditary form of lymphedema with autosomal dominant inheritance. Individuals With Milroy disease are typically characterized by congenital onset of lymphedema of the lower limbs due to hypoplasia of the lymphatic vessels. The genetic basis of most cases of Milroy disease has not been established, although mutations in the vascular endothelial growth factor receptor VIEGFR3 (FLT-4) are responsible for some cases with 17 mutations described to date. in this report, we describe a novel VEGFK3 mutation in exon 22 in a four-generation family in which congenital lymphedema segregates in an autosomal dominant manner. in addition to lymphedema, affected family members had other clinical manifestations associated with Milroy disease including hydrocele, ski jump toenails, large caliber veins, and subcutaneous thickening. We screened VEGFR3 for mutations which revealed a novel 3059A > T transversion in exon 22 resulting in Q1020L missense mutation in the second tyrosine kinase domain of VEGFR3. This mutant allele segregated with lymphedema among affected individuals with incomplete penetrance. This is the first report of an exon 22 mutation in Milroy disease. (c) 2007 Wiley-Liss, Inc.