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RASA 1 Mutations and Associated Phenotypes in 68 Families with Capillary Malformation–Arteriovenous Malformation
Author(s) -
Revencu Nicole,
Boon Laurence M.,
Mendola Antonella,
Cordisco Maria Rosa,
Dubois Josée,
Clapuyt Philippe,
Hammer Frank,
Amor David J.,
Irvine Alan D.,
Baselga Eulalia,
Dompmartin Anne,
Syed Samira,
MartinSantiago Ana,
Ades Lesley,
Collins Felicity,
Smith Janine,
Sandaradura Sarah,
Barrio Victoria R.,
Burrows Patricia E.,
Blei Francine,
Cozzolino Mariarosaria,
BrunettiPierri Nicola,
Vicente Asuncion,
Abramowicz Marc,
Désir Julie,
Vilain Catheline,
Chung Wendy K.,
Wilson Ashley,
Gardiner Carol A.,
Dwight Yim,
Lord David J.E.,
Fishman Leona,
Cytrynbaum Cheryl,
Chamlin Sarah,
Ghali Fred,
Gilaberte Yolanda,
Joss Shelagh,
Boente Maria del C.,
LéautéLabrèze Christine,
Delrue MarieAnge,
Bayliss Susan,
Martorell Loreto,
GonzálezEnseñat MariaAntonia,
MazereeuwHautier Juliette,
O'Donnell Brid,
Bessis Didier,
Pyeritz Reed E.,
Salhi Aicha,
Tan Oon T.,
Wargon Orli,
Mulliken John B.,
Vikkula Miikka
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22431
Subject(s) - phenotype , arteriovenous malformation , port wine stain , biology , germline mutation , mutation , vascular malformation , clinical phenotype , pathology , allele , germline , genetics , medicine , radiology , gene , laser , physics , optics
Capillary malformation–arteriovenous malformation ( CM – AVM ) is an autosomal‐dominant disorder, caused by heterozygous RASA 1 mutations, and manifesting multifocal CM s 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. RASA 1 was screened in 261 index patients with: CM – AVM ( n = 100), common CM (s) (port‐wine stain; n = 100), S turge– W eber syndrome ( n = 37), or isolated AVM (s) ( n = 24). Fifty‐eight distinct RASA 1 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 RASA 1 mutation was available. The analysis of the tissue showed loss of the wild‐type RASA 1 allele. In conclusion, mutations in RASA 1 underscore the specific CM – AVM phenotype and the clinical diagnosis is based on identifying the characteristic CM s. The high incidence of fast‐flow lesions warrants careful clinical and radiologic examination, and regular follow‐up.