一成骨不全家系的COL1A1基因突变检测  

Mutation Detection of COL1A1 Gene in a Pedigree with Osteogenesis Imperfecta

作　　者：秦炜[1] 何隽祥 施瑾[3] 邢清和[1] 高建军[4] 钱学庆[4] 刘壮俊[1] 舒安利[5] 贺林[1] 

机构地区：[1]上海交通大学Bio-X生命科学研究中心,上海200030 [2]甘肃省张掖地区医院放射科,张掖734000 [3]浙江大学医学院附属第一医院,杭州310003 [4]中国科学院上海生命科学研究院营养科学研究所,上海200031 [5]湖南怀化医学高等专科学校,怀化418000

出　　处：《Acta Genetica Sinica》2005年第3期248-252,共5页

基　　金：国家科技攻关计划(编号:2002BA711A070);国家自然科学基金(编号:30130250)资助项目~~

摘　　要：成骨不全(Osteogenesisimperfecta,OI)是一种由于Ⅰ型胶原形成障碍,导致骨脆性增强为主要症状的 常染色体显性遗传性疾病。临床上主要表现为骨质脆弱、蓝巩膜、耳聋和中等程度的关节畸形等症状。成骨不全 基因分别定位于17q21.31 q22和7q22.1,其致病基因分别为COL1A1和COL1A2。对一常染色体显性遗传的 成骨不全家系进行连锁分析,在COL1A1遗传位点发现紧密连锁(LOD=9.31;θ=.00)。突变检测发现在 COL1A1基因第26内含子5′端剪接位点处存在一由GT转换为AT的致病突变,该突变引起的异常剪接是导致成 骨不全的致病原因之一。Osteogenesis imperfecta(OI)is heritable bone fragility,which is inherited as an autosomal dominant trait clinical presentation.Clinical symptom,in general,is dominantly inherited OI with blue sclerae,hearing loss and mild-moderate skeletal deformity.Genetic loci of OI have been mapped to17q21.31-q22 and 7q22.1,in which COL1A1 and COL1A2 are known to be the causal genes.In this work,we performed linkage analysis in a kindred with autosomal dominant hereditary OI.A tight linkage to the markers on chromosome 17q21.31-q22 (maximum two-point lod score:9.31 at θ=.00) was observed.Sequence analysis of COL1A1 revealed a single-base mutation that converted the consensus sequence at the 5′end of intron 26 from GT to AT to form an abnormal splicing site leading to OI.

关 键 词：成骨不全 连锁分析 突变 剪接位点 

分 类 号：R681.1[医药卫生—骨科学]