title: Cerebral cavernous malformation: novel mutation in a Chinese family and evidence for heterogeneity.
abstract: Familial cerebral cavernous malformation (CCM) is an autosomal dominant disorder producing vascular anomalies throughout the central nervous system associated with seizures and hemorrhagic stroke. Linkage analysis has shown evidence for at least three genetic loci underlying this disorder with a founder mutation in the Mexican/Hispanic community. We report the first family of Chinese ethnic origin with CCM having a novel mutation in the CCM1 gene. The mutation in exon 19 causes a premature stop codon (Q698X) predicted to produce a truncated Krev1 interaction-trapped 1 (KRIT1) protein. Members of the family with this mutation have a wide range in age of onset with seizures, ataxia, spinal cord vascular malformation, headaches and skin lesions. An additional unrelated sporadic subject with brain lesions compatible with CCM as well as vascular skin findings suggesting the blue rubber bleb nevus (BRBN) syndrome has no mutation detected in the CCM1 gene. These findings expand the phenotype of and demonstrate further evidence for the heterogeneity in the CCM syndrome.
authors.affiliation: Department of Neurology, University of Washington, Seattle, WA, USA.
authors.forename: Dong-Hui
authors.initials: DH
authors.lastname: Chen
authors.forename: Hillary P
authors.initials: HP
authors.lastname: Lipe
authors.forename: Zhen
authors.initials: Z
authors.lastname: Qin
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Bird
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology; D002536:Cerebral Arteries / Q000473:pathology* / Q000503:physiopathology; D002648:Child; D002681:China; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D018389:Codon, Nonsense / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D014644:Genetic Variation / Q000502:physiology*; D020786:Hemangioma, Cavernous, Central Nervous System / Q000235:genetics* / Q000473:pathology; D006801:Humans; D000075927:KRIT1 Protein; D008297:Male; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins; D008875:Middle Aged; D009506:Nevus / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018389:Codon, Nonsense; D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins; D008780:Methyltransferases; C055097:mRNA (guanine(N7))-methyltransferase