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Family Linkage Analysis of CCM1 Locus on Chromosome 7q in Familial Cavernous Malformation  

Sim Ki-Bum (Department of Neurosurgery, College of Medicine, Cheju National University)
Lee Chang Sub (Department of Neurosurgery, College of Medicine, Cheju National University)
Kim Seung-Ki (Division of Pediatric Neurosurgery and Clinical Research Institute, Seoul National University Children's Hospital)
Wang Kyu-Chang (Division of Pediatric Neurosurgery and Clinical Research Institute, Seoul National University Children's Hospital)
Kim Young-Im (Neuroscience Research Institute, SNUMRC)
Cho Byung-Kyu (Division of Pediatric Neurosurgery and Clinical Research Institute, Seoul National University Children's Hospital)
Publication Information
Toxicological Research / v.21, no.2, 2005 , pp. 135-140 More about this Journal
Abstract
Although the pathogenesis of cerebral cavernous malformation (CCM) is unknown, a familial predisposition has been recognized, with up to $55\%$ of patients having an affected relatives. Genetic linkage studies have recently mapped a gene causing CCM to a segment of the long arm of chromosome 7 (7q). We report herein a genetic linkage analysis conducted on a Korean three generation family with CCM. It's first report in Korean family. A Korean family in which one member had undergone surgery for ubtracerebrak hematoma (ICH) and confirmed the CCM, was evaluated. They were examined clinically (n=18) and by magnetic resonance (MR) imaging (n=10). Polymorphic markers (D7S1813, D7S1789) spanning the CCM1 locus on 7q were genotyped by the polymerase chain reaction and analysis of linkage was performed in this family (n=17). Six had multiple lesions on brain MR image, one of them being symptomatic, and five were asymptomatic. Seven remaining members were asymptomatic and refused MR image study. One had died of ICH from presumed CCM. Analysis of the pedigree was consistent with an autosomal dominant pattern of inheritance. All affected patients were linked to CCM1. Linkage to CCM1 can account for inheritance of CCM in this family. They had some striking features with a low clinical penetrance and the presence of multiple lesions. These findings have implications for genetic testing of this disorder and represent an important step toward identification of the gene responsible for the pathogenesis of this disease.
Keywords
Familial cavernous malformation; Chromosome 7; CCM1 locus; Autosomal domina pattern; Genetic linkage analysis.;
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