Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema
Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema
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DOI：
10.1038/75997
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发表时间：
2000-06-01
期刊：
影响因子：
30.8
通讯作者：
Finegold, DN
中科院分区：
文献类型：
--
作者：
Karkkainen, MJ;Ferrell, RE;Finegold, DN
原发性淋巴水肿是一种罕见的常染色体显性遗传疾病，会导致四肢残疾和毁容肿胀，如果不治疗，往往会随着时间的推移而恶化。在这里，我们将原发性人类淋巴水肿与编码血管内皮生长因子受体 3 (VEGFR-3) 的 FLT4 基因座联系起来。在几个家庭中。分析的所有疾病相关等位基因均存在错义突变，并编码具有失活酪氨酸激酶的蛋白质，从而阻止下游基因激活。我们的研究证实，VEGFR-3 对于正常淋巴血管功能很重要，并且干扰 VEGFR-3 信号转导的突变是原发性淋巴水肿的原因。
Primary lymphoedema is a rare, autosomal dominant disorder that leads to a disabling and disfiguring swelling of the extremities and, when untreated, tends to worsen with time. Here we link primary human lymphoedema to the FLT4 locus, encoding vascular endothelial growth factor receptor-3 (VEGFR-3). in several families. All disease-associated alleles analysed had missense mutations and encoded proteins with an inactive tyrosine kinase, preventing downstream gene activation, Our study establishes that VEGFR-3 is important for normal lymphatic vascular function and that mutations interfering with VEGFR-3 signal transduction are a cause of primary lymphoedema.