成骨不全4个家系基因突变检测及表型与基因型的关系

Detection of Gene Mutation and Relationship between Phenotype and Genotype in Four Chinese Families with Osteogenesis Imperfecta

目的对国内4个成骨不全(OI)家系进行临床调查分析和基因突变检测,探讨中国人群OI基因型与表型的关系。方法分别对4例来自不同家系的OI先证者进行体格检查及家系调查,收集临床资料及血液标本,绘制家系图谱,确定各家系成员患病个体的临床诊断分型。提取其血液标本基因组DNA,应用PCR扩增及DNA直接测序法对4例先证者Ⅰ型胶原基因进行基因突变检测,并应用生物信息学软件对测序结果与Genbank标准序列进行对比;根据先证者检测结果,分别对各家系成员进行COL1A1/COL1A2基因突变检测和分析。结果在先证者1及家系患病个体中检测到COL1A1基因第36外显子c.2473位点G>A突变,在先证者2COL1A1基因上第26内含子剪切位点处c.1821+1G>A突变,在先证者4及家系患病个体中检测到COL1A1基因第9内含子剪切位点处c.697-2A>T突变,先证者3及4个家系非患病成员均未检测到COL1A1/COL1A2基因突变。结论COL1A1基因突变是引起中国人群OI的原因之一,但还可能有其他的基因突变存在,临床表型不仅与基因型有关,还可能受遗传背景、环境及其他因素的影响。

Objective To study the relationship between phenotype and genotype in 4 Chinese families with osteogenesis imperfecta（OI） by clinical analysis and gene mutation detection.Methods Clinical examination and family survey were used respectively to decide clinical classification in the 4 families with OI.Firstly,the clinical data and blood samples were collected and the family maps were drawn to determine the clinical types;then genomic DNA was extracted from blood samples.Secondly,Polymerase chain reaction and DNA sequencing were used to check the 4 proposituses with OI and the mutation of COL1A1 and COL1A2 genes,then the sequencing result and Genbank stan-dard seguencing were compared and analyzed by bioinformatic software.According to the result of detection to propositus,the COL1A1/COL1A2 genetic mutation for all family members were detected and analyzed.Results A c.2473GA mutation was detected in the 36th exon of COL1A1 gene of the first propositus and the OI patients of the family,c.1821＋1GA mutation was deteced at the shearing site of the 26th intron of COL1A1 gene in the second propositus,and c.697-2CT mutation was detected in the 4th propositus at the 9th intron,but any COL1A1 or COL1A2 gene mutation was detected in the third propositus and the other members in the former families.Conclusions The genetic mutation of COL1A1 may result in OI in China,but other mutations may also exist.Moreover,the phenotype was influenced not only by OI genotype,but also by the genetic background,environment and other factors.