一中国脑海绵状血管瘤家系中发现krit1基因新的缺失突变(英文)  

A Novel Deletion Mutation in CCM1 Gene (krit1) is Detected in a Chinese Family with Cerebral Cavernous Malformations

作　　者：纪宝虎[1] 秦炜[2] 孙涛[3] 冯国鄞[2] 贺林[2] 王玉炯[1] 

机构地区：[1]宁夏大学生命科学学院生物技术重点实验室,银川750021 [2]上海交通大学Bio-X生命科学研究中心,上海200030 [3]宁夏医学院,银川750004

出　　处：《Acta Genetica Sinica》2006年第2期105-110,共6页

基　　金：This work was supported by the Technology Research Major Program of Ministry of Education of China ( No. 205172)

摘　　要：脑海绵状血管瘤(CCM)是多定位于中枢神经系统的一种脑部血管异常,少数在皮肤和视网膜处有并发症。依据致病基因在染色体上的不同位置分为 CCM1、CCM2 和 CCM3 3 种类型。目前,CCM1、CCM2 和 CCM3 的致病基因已经被克隆,分别为 krit1、MGC4607 和细胞程序性死亡 10 基因(PDCD10)。利用连锁分析发现内蒙古的一个家系属于 CCM1,突变检测发现患者 CCM1 基因(krit1)第 9 内含子和第 10 外显子拼接位点处存在一“GTA”缺失,该突变导致终止密码子提前出现,产生截短蛋白。实验结果支持 krit1 为 CCM1 致病基因。Cerebral Cavernous Malformations （CCM） are vascular malformations that are mostly located in the central nervous system （CNS） and occasionally within the skin and retina, which are classified into three types （CCM1, CCM2 and CCM3） by being located at different loci on chromosomes. At present, CCM1 （7q21）, CCM2 （7p13-p15） and CCM3 （3q25.2-q27） are respectively linked to kritl （Krev interaction trapped gene 1）, MGC4607 and PDCDIO （programmed cell death 10）. In this work, we identified a novel ＂GTA＂ deletion mutation at the acceptor splicing site of intron9/exon10 on kritl. The mutation results in an abnormally spliced protein by creating a premature termination code at the 23rd amino acid downstream from the sequence alteration. Our results are consistent with previous research on kritl mutations and confirm the conclusion that KRIT1 haploinsufficiency may be the underlying mechanism of CCM1.

关 键 词：脑海绵状血管瘤(CCM) krit1 突变 连锁分析 

分 类 号：R739.41[医药卫生—肿瘤]