title: Parkes Weber syndrome, vein of Galen aneurysmal malformation, and other fast-flow vascular anomalies are caused by RASA1 mutations.
abstract: Capillary malformation-arteriovenous malformation (CM-AVM) is a newly recognized autosomal dominant disorder, caused by mutations in the RASA1 gene in six families. Here we report 42 novel RASA1 mutations and the associated phenotype in 44 families. The penetrance and de novo occurrence were high. All affected individuals presented multifocal capillary malformations (CMs), which represent the hallmark of the disorder. Importantly, one-third had fast-flow vascular lesions. Among them, we observed severe intracranial AVMs, including vein of Galen aneurysmal malformation, which were symptomatic at birth or during infancy, extracranial AVM of the face and extremities, and Parkes Weber syndrome (PKWS), previously considered sporadic and nongenetic. These fast-flow lesions can be differed from the other two genetic AVMs seen in hereditary hemorrhagic telangiectasia (HHT) and in phosphatase and tensin homolog (PTEN) hamartomatous tumor syndrome. Finally, some CM-AVM patients had neural tumors reminiscent of neurofibromatosis type 1 or 2. This is the first extensive study on the phenotypes associated with RASA1 mutations, and unravels their wide heterogeneity.
authors.affiliation: Laboratory of Human Molecular Genetics, de Duve Institute, 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: John B
authors.initials: JB
authors.lastname: Mulliken
authors.forename: Odile
authors.initials: O
authors.lastname: Enjolras
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Cordisco
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Burrows
authors.forename: Philippe
authors.initials: P
authors.lastname: Clapuyt
authors.forename: Frank
authors.initials: F
authors.lastname: Hammer
authors.forename: Josée
authors.initials: J
authors.lastname: Dubois
authors.forename: Eulalia
authors.initials: E
authors.lastname: Baselga
authors.forename: Francesco
authors.initials: F
authors.lastname: Brancati
authors.forename: Robin
authors.initials: R
authors.lastname: Carder
authors.forename: José Miguel Ceballos
authors.initials: JM
authors.lastname: Quintal
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: Gayle
authors.initials: G
authors.lastname: Fischer
authors.forename: Ilona J
authors.initials: IJ
authors.lastname: Frieden
authors.forename: Maria
authors.initials: M
authors.lastname: Garzon
authors.forename: John
authors.initials: J
authors.lastname: Harper
authors.forename: Jennifer
authors.initials: J
authors.lastname: Johnson-Patel
authors.forename: Christine
authors.initials: C
authors.lastname: Labrèze
authors.forename: Loreto
authors.initials: L
authors.lastname: Martorell
authors.forename: Harriet J
authors.initials: HJ
authors.lastname: Paltiel
authors.forename: Annette
authors.initials: A
authors.lastname: Pohl
authors.forename: Julie
authors.initials: J
authors.lastname: Prendiville
authors.forename: Isabelle
authors.initials: I
authors.lastname: Quere
authors.forename: Dawn H
authors.initials: DH
authors.lastname: Siegel
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Valente
authors.forename: Annet
authors.initials: A
authors.lastname: Van Hagen
authors.forename: Liselot
authors.initials: L
authors.lastname: Van Hest
authors.forename: Keith K
authors.initials: KK
authors.lastname: Vaux
authors.forename: Asuncion
authors.initials: A
authors.lastname: Vicente
authors.forename: Lisa
authors.initials: L
authors.lastname: Weibel
authors.forename: David
authors.initials: D
authors.lastname: Chitayat
authors.forename: Miikka
authors.initials: M
authors.lastname: Vikkula
mesh_terms: D001165:Arteriovenous Malformations; D005190:Family; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D011994:Recombinant Proteins / Q000235:genetics*; D057127:Single-Chain Antibodies; D013577:Syndrome; D054079:Vascular Malformations / Q000235:genetics*; D054080:Vein of Galen Malformations / Q000235:genetics*; D020729:p120 GTPase Activating Protein
chemical_list: D007135:Immunoglobulin Variable Region; C557248:RASA1 protein, human; D011994:Recombinant Proteins; D057127:Single-Chain Antibodies; D020729:p120 GTPase Activating Protein