Genetics of lymphatic anomalies

被引：241

作者：

Brouillard, Pascal ^{[1
]}

Boon, Laurence ^{[1
,2
]}

Vikkula, Miikka ^{[1
,2
,3
]}

机构：

[1] Catholic Univ Louvain, De Duve Inst, Lab Human Mol Genet, B-1200 Brussels, Belgium

[2] Catholic Univ Louvain, Clin Univ St Luc, Ctr Vasc Anomalies, Div Plast Surg, B-1200 Brussels, Belgium

[3] Catholic Univ Louvain, Walloon Excellence Lifesci & Biotechnol, B-1200 Brussels, Belgium

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2014年 / 124卷 / 03期

关键词：

GROWTH-FACTOR-C; NF-KAPPA-B; PRIMARY LYMPHEDEMA; CONGENITAL LYMPHEDEMA; SECONDARY LYMPHEDEMA; ECTODERMAL DYSPLASIA; TRANSCRIPTION FACTOR; MISSENSE MUTATION; MILROY-DISEASE; MICE LACKING;

D O I：

10.1172/JCI71614

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Lymphatic anomalies include a variety of developmental and/or functional defects affecting the lymphatic vessels: sporadic and familial forms of primary lymphedema, secondary lymphedema, chylothorax and chylous ascites, lymphatic malformations, and overgrowth syndromes with a lymphatic component. Germline mutations have been identified in at least 20 genes that encode proteins acting around VEGFR-3 signaling but also downstream of other tyrosine kinase receptors. These mutations exert their effects via the RAS/MAPX and the PI3K/AKT pathways and explain more than a quarter of the incidence of primary lymphedema, mostly of inherited forms. More common forms may also result from multigenic effects or post-zygotic mutations. Most of the corresponding murine knockouts are homozygous lethal, while heterozygotes are healthy, which suggests differences in human and murine physiology and the influence of other factors.

引用

页码：898 / 904

页数：7

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