title: RASA1 mutations and associated phenotypes in 68 families with capillary malformation-arteriovenous malformation.
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.
authors.affiliation: Laboratory 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.
authors.forename: Nicole
authors.initials: N
authors.lastname: Revencu
authors.forename: Laurence M
authors.initials: LM
authors.lastname: Boon
authors.forename: Antonella
authors.initials: A
authors.lastname: Mendola
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Cordisco
authors.forename: Josée
authors.initials: J
authors.lastname: Dubois
authors.forename: Philippe
authors.initials: P
authors.lastname: Clapuyt
authors.forename: Frank
authors.initials: F
authors.lastname: Hammer
authors.forename: David J
authors.initials: DJ
authors.lastname: Amor
authors.forename: Alan D
authors.initials: AD
authors.lastname: Irvine
authors.forename: Eulalia
authors.initials: E
authors.lastname: Baselga
authors.forename: Anne
authors.initials: A
authors.lastname: Dompmartin
authors.forename: Samira
authors.initials: S
authors.lastname: Syed
authors.forename: Ana
authors.initials: A
authors.lastname: Martin-Santiago
authors.forename: Lesley
authors.initials: L
authors.lastname: Ades
authors.forename: Felicity
authors.initials: F
authors.lastname: Collins
authors.forename: Janine
authors.initials: J
authors.lastname: Smith
authors.forename: Sarah
authors.initials: S
authors.lastname: Sandaradura
authors.forename: Victoria R
authors.initials: VR
authors.lastname: Barrio
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Burrows
authors.forename: Francine
authors.initials: F
authors.lastname: Blei
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Cozzolino
authors.forename: Nicola
authors.initials: N
authors.lastname: Brunetti-Pierri
authors.forename: Asuncion
authors.initials: A
authors.lastname: Vicente
authors.forename: Marc
authors.initials: M
authors.lastname: Abramowicz
authors.forename: Julie
authors.initials: J
authors.lastname: Désir
authors.forename: Catheline
authors.initials: C
authors.lastname: Vilain
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
authors.forename: Ashley
authors.initials: A
authors.lastname: Wilson
authors.forename: Carol A
authors.initials: CA
authors.lastname: Gardiner
authors.forename: Yim
authors.initials: Y
authors.lastname: Dwight
authors.forename: David J E
authors.initials: DJ
authors.lastname: Lord
authors.forename: Leona
authors.initials: L
authors.lastname: Fishman
authors.forename: Cheryl
authors.initials: C
authors.lastname: Cytrynbaum
authors.forename: Sarah
authors.initials: S
authors.lastname: Chamlin
authors.forename: Fred
authors.initials: F
authors.lastname: Ghali
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Gilaberte
authors.forename: Shelagh
authors.initials: S
authors.lastname: Joss
authors.forename: Maria Del C
authors.initials: Mdel C
authors.lastname: Boente
authors.forename: Christine
authors.initials: C
authors.lastname: Léauté-Labrèze
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Delrue
authors.forename: Susan
authors.initials: S
authors.lastname: Bayliss
authors.forename: Loreto
authors.initials: L
authors.lastname: Martorell
authors.forename: Maria-Antonia
authors.initials: MA
authors.lastname: González-Enseñat
authors.forename: Juliette
authors.initials: J
authors.lastname: Mazereeuw-Hautier
authors.forename: Brid
authors.initials: B
authors.lastname: O'Donnell
authors.forename: Didier
authors.initials: D
authors.lastname: Bessis
authors.forename: Reed E
authors.initials: RE
authors.lastname: Pyeritz
authors.forename: Aicha
authors.initials: A
authors.lastname: Salhi
authors.forename: Oon T
authors.initials: OT
authors.lastname: Tan
authors.forename: Orli
authors.initials: O
authors.lastname: Wargon
authors.forename: John B
authors.initials: JB
authors.lastname: Mulliken
authors.forename: Miikka
authors.initials: M
authors.lastname: Vikkula
mesh_terms: D019943:Amino Acid Substitution; D001165:Arteriovenous Malformations / Q000175:diagnosis* / Q000235:genetics*; D002196:Capillaries / Q000002:abnormalities*; D004252:DNA Mutational Analysis; D005260:Female; D023061:Gene Order; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D019339:Port-Wine Stain / Q000175:diagnosis* / Q000235:genetics*; D011446:Prospective Studies; D012189:Retrospective Studies; D020729:p120 GTPase Activating Protein / Q000235:genetics*
chemical_list: C557248:RASA1 protein, human; D020729:p120 GTPase Activating Protein
keywords: RASA1; Sturge-Weber syndrome; arteriovenous malformation; capillary malformation