一个I型成骨不全家系COLlAl基因的剪切位点新突变及产前诊断  

Mutation analysis and prenatal diagnosis of COL1A1 gene in a Chinese family with type I osteogenesis imperfecta

作　　者：张卉[1] 吴东[1] 侯巧芳[1] 刘治佑[1] 秦利涛[1] 廖世秀[1] 

机构地区：[1]郑州大学人民医院,河南省人民医院临床基因诊断与基因治疗院士工作站,450003

出　　处：《中华医学遗传学杂志》2014年第6期730-732,共3页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金（81170581）

摘　　要：目的确定1个汉族成骨不全家系COLIAl基因的突变情况，为家系胎儿提供产前诊断。方法应用测序方法对家系成员及100名正常对照者的COLlAl和COLlA2基因进行突变检测。结果基因测序结果显示先证者及家系中7例存活患者的COLIAl基因的剪接位点存在C．104—1G〉C突变，但是在正常家系成员以及100名无亲缘关系的正常对照中均未检测到该突变。经查询I型胶原突变数据库该突变为未报道过的新突变。该家系所有成员COLIA2基因未检测到突变。胎儿的COLlAI基因测序结果正常，随访时的基因突变检测结果与产前诊断结果一致。结论COLlAl基因C．104～1G〉C突变是该家系的致病原因，在明确致病突变基因的前提下可对家系胎儿进行产前诊断，以避免成骨不全患儿的出生。Objective To detect mutation of COL1A1 gene in a Chinese family affected with type I osteogenesis imperfecta （OI） and to provide prenatal diagnosis for a fetus at 17th gestational week. Methods Polymerase chain reaction, DNA sequencing and restriction endonuclease analysis were used to verify the detected mutation among other members of the family and 100 healthy controls. Results No mutation has been detected in the COL1A2 gene in all of the subjects. A heterozygous mutation c. 104-1G〉C was identified in the COL1A1 gene among all patients from this family. The same mutation was not found in other members from the family and the 100 healthy controls. The mutation was not found in the fetus, and was verified to be a new mutation according to the type I collagen mutation database. Conclusion The c. 104-1G〉C mutation of the COL1A1 gene probably underlies the type I osteogenesis imperfecta in this family. Under the premise of a clear genetic diagnosis, prenatal diagnosis may be provided to reduce the risk for the disease.

关 键 词：成骨不全 COL1A1基因 基因突变 产前诊断 

分 类 号：R440[医药卫生—诊断学]