title: Mutations in a gene encoding a novel protein containing a phosphotyrosine-binding domain cause type 2 cerebral cavernous malformations.
abstract: Cerebral cavernous malformations (CCMs) are congenital vascular anomalies of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. Mutations in the gene KRIT1 are responsible for type 1 CCM (CCM1). We report that a novel gene, MGC4607, exhibits eight different mutations in nine families with type 2 CCM (CCM2). MGC4607, similar to the KRIT1 binding partner ICAP1alpha, encodes a protein with a phosphotyrosine-binding domain. This protein may be part of the complex pathway of integrin signaling that, when perturbed, causes abnormal vascular morphogenesis in the brain, leading to CCM formation.
authors: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
authors: Christina L
authors: CL
authors: Liquori
authors: Michel J
authors: MJ
authors: Berg
authors: Adrian M
authors: AM
authors: Siegel
authors: Elizabeth
authors: E
authors: Huang
authors: Jon S
authors: JS
authors: Zawistowski
authors: T'Prien
authors: T
authors: Stoffer
authors: Dominique
authors: D
authors: Verlaan
authors: Fiyinfolu
authors: F
authors: Balogun
authors: Lori
authors: L
authors: Hughes
authors: Tracey P
authors: TP
authors: Leedom
authors: Nicholas W
authors: NW
authors: Plummer
authors: Milena
authors: M
authors: Cannella
authors: Vittorio
authors: V
authors: Maglione
authors: Ferdinando
authors: F
authors: Squitieri
authors: Eric W
authors: EW
authors: Johnson
authors: Guy A
authors: GA
authors: Rouleau
authors: Louis
authors: L
authors: Ptacek
authors: Douglas A
authors: DA
authors: Marchuk
mesh_terms: D015152:Blotting, Northern; D001921:Brain / Q000196:embryology*; D020785:Central Nervous System Vascular Malformations / Q000235:genetics*; D002874:Chromosome Mapping; D020022:Genetic Predisposition to Disease; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D000075927:KRIT1 Protein; D008279:Magnetic Resonance Imaging; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009024:Morphogenesis; D009154:Mutation / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D015398:Signal Transduction
chemical_list: D016023:Integrins; D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins