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

Center for Human Genetics, Cliniques universitaires St Luc, Université catholique de Louvain, Brussels, Belgium.
Human Mutation (Impact Factor: 5.05). 08/2013; DOI: 10.1002/humu.22431
Source: PubMed

ABSTRACT Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal dominant disorder, caused by heterozygous RASA1 mutations, and manifesting multifocal capillary malformations and high risk for fast-flow lesions. A limited number of patients has 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 capillary malformation(s) (port-wine stain; n = 100), Sturge-Weber syndrome (n = 37), or isolated arteriovenous malformation(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 capillary malformations. The high incidence of fast-flow lesions warrants careful clinical and radiologic examination, and regular follow-up. This article is protected by copyright. All rights reserved.

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