title: A NovelCCM2Gene Mutation Associated with Familial Cerebral Cavernous Malformation.
abstract: Background:Cerebral cavernous malformations (CCMs) are common vascular malformations that predominantly arise in the central nervous system and are mainly characterized by enlarged vascular cavities without intervening brain parenchyma. Familial CCMs (FCCMs) is inherited in an autosomal dominant pattern with incomplete penetrance and variable symptoms.Methods:Mutations of three pathogenic genes,CCM1, CCM2, andCCM3, were investigated by direct DNA sequencing in a Chinese family with multiple CCM lesions.Results:Four heterozygous variants in theCCM2gene, including one deletion (c.95delC), a missense mutation (c.358G>A, p.V120I), one silent mutation (c.915G>A, p.T305T), and a substitution (c.*1452 T>C), were identified in the subjects with multiple CCM lesions, but not in a healthy sibling. Among these variants, the c.95delC deletion is a novel mutation which is expected to cause a premature termination codon. It is predicted to produce a truncatedCCM2protein lacking the PTB and C-terminal domains, thus disrupting the molecular functions ofCCM2.Conclusions:The novel truncating mutation in theCCM2gene, c.95delC, may be responsible for multiple CCM lesions in a part of FCCM. In addition, it may represent a potential genetic biomarker for early diagnosis of FCCM.
authors.affiliation: Translational Medicine Research Center, School of Pharmaceutical Sciences, Xiamen UniversityXiamen, China; Key Laboratory for Cancer T-Cell Theranostics and Clinical TranslationXiamen, China.
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Huang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Xiamen University Xiamen, China.
authors.forename: Cong-Xia
authors.initials: CX
authors.lastname: Lu
authors.affiliation: Translational Medicine Research Center, School of Pharmaceutical Sciences, Xiamen UniversityXiamen, China; Key Laboratory for Cancer T-Cell Theranostics and Clinical TranslationXiamen, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Xiamen UniversityXiamen, China; The First Clinical College of Fujian Medical UniversityFuzhou, China.
authors.forename: Ke-Hui
authors.initials: KH
authors.lastname: Yi
authors.affiliation: Translational Medicine Research Center, School of Pharmaceutical Sciences, Xiamen UniversityXiamen, China; Key Laboratory for Cancer T-Cell Theranostics and Clinical TranslationXiamen, China.
authors.forename: Liang-Liang
authors.initials: LL
authors.lastname: Cai
authors.affiliation: Translational Medicine Research Center, School of Pharmaceutical Sciences, Xiamen UniversityXiamen, China; Key Laboratory for Cancer T-Cell Theranostics and Clinical TranslationXiamen, China.
authors.forename: Ming-Li
authors.initials: ML
authors.lastname: Li
authors.affiliation: Translational Medicine Research Center, School of Pharmaceutical Sciences, Xiamen UniversityXiamen, China; Key Laboratory for Cancer T-Cell Theranostics and Clinical TranslationXiamen, China.
authors.forename: Han
authors.initials: H
authors.lastname: Wang
authors.affiliation: Translational Medicine Research Center, School of Pharmaceutical Sciences, Xiamen UniversityXiamen, China; Department of Neurology, The First Affiliated Hospital of Xiamen UniversityXiamen, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Translational Medicine Research Center, School of Pharmaceutical Sciences, Xiamen UniversityXiamen, China; Key Laboratory for Cancer T-Cell Theranostics and Clinical TranslationXiamen, China; INNOVA Cell: TDx/Clinics and TRANSLATE Health GroupYangzhou, China.
authors.forename: Chi-Meng
authors.initials: CM
authors.lastname: Tzeng
keywords: CCM2; biomarker; familial cerebral cavernous malformations (FCCM); mutation; pathogenesis; susceptibility-weighted imaging (SWI)