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Hum Mutat. 2013 Dec;34(12):1632-41. doi: 10.1002/humu.22431. Epub 2013 Oct 10.

RASA1 mutations and associated phenotypes in 68 families with capillary malformation-arteriovenous malformation.

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  • 1Laboratory of Human Molecular Genetics, de Duve Institute, Université catholique de Louvain, Brussels, Belgium; Center for Human Genetics, Cliniques universitaires St Luc, Université catholique de Louvain, Brussels, Belgium.

Abstract

Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal-dominant disorder, caused by heterozygous RASA1 mutations, and manifesting multifocal CMs and high risk for fast-flow lesions. A limited number of patients have been reported, raising the question of the phenotypic borders. We identified new patients with a clinical diagnosis of CM-AVM, and patients with overlapping phenotypes. RASA1 was screened in 261 index patients with: CM-AVM (n = 100), common CM(s) (port-wine stain; n = 100), Sturge-Weber syndrome (n = 37), or isolated AVM(s) (n = 24). Fifty-eight distinct RASA1 mutations (43 novel) were identified in 68 index patients with CM-AVM and none in patients with other phenotypes. A novel clinical feature was identified: cutaneous zones of numerous small white pale halos with a central red spot. An additional question addressed in this study was the "second-hit" hypothesis as a pathophysiological mechanism for CM-AVM. One tissue from a patient with a germline RASA1 mutation was available. The analysis of the tissue showed loss of the wild-type RASA1 allele. In conclusion, mutations in RASA1 underscore the specific CM-AVM phenotype and the clinical diagnosis is based on identifying the characteristic CMs. The high incidence of fast-flow lesions warrants careful clinical and radiologic examination, and regular follow-up.

© 2013 WILEY PERIODICALS, INC.

KEYWORDS:

RASA1; Sturge-Weber syndrome; arteriovenous malformation; capillary malformation

PMID:
24038909
[PubMed - indexed for MEDLINE]
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