六个成骨不全家系的临床表型分析及基因变异检测  

Phenotype-genotype analysis and detection of gene variant in six families with osteogenesis imperfecta

作　　者：侯瑞 李闯 刘彩霞[1] 李欢[1] 李岭 吕远[1] 张志涛[1] Hou Rui;Li Chuang;Liu Caixia;Li Huan;Li-Ling;Lyu Yuan;Zhang Zhitao(Department of Gynecology and Obstetrics,Shengjing Hospital Affiliated to China Medical University,Key Laboratory of Maternal-Fetal Medicine of Liaoning Province,Shenyang,Liaoning 110004,China;State Key Laboratory of Biotherapy,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,China)

机构地区：[1]中国医科大学附属盛京医院妇产科,辽宁省母胎医学重点实验室,沈阳110004 [2]四川大学华西医院生物治疗国家重点实验室,成都610041

出　　处：《中华医学遗传学杂志》2020年第5期514-518,共5页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(81701462,81501260);中央引导地方科技发展专项资金(2016007014);盛京自由研究者基金(201501)。

摘　　要：目的分析6个成骨不全家系的临床表型并明确其致病变异,为遗传咨询及产前诊断提供依据。方法收集6个家系的临床资料以及外周血或引产组织样本,应用二代测序(next generation sequencing,NGS)技术对先证者的全部基因进行检测,用PCR反应扩增检出的变异位点,之后进行Sanger测序。在6个家系的所有成员以及100名健康对照中对检测到的变异位点进行验证。结果家系1的先证者及其女儿携带COL1A1基因c.1976G>C杂合变异,家系2~6的先证者分别携带COL1A2基因c.2224G>A、COL1A1基因c.2533G>A、COL1A2基因c.2845G>A、COL1A1基因c.2532_2540delCGGACCCGC以及COL1A2基因c.1847G>A杂合变异。先证者的双亲均未携带相应变异,在100名健康对照中均未检测到上述变异。结论6个成骨不全家系的致病原因可能均为COL1A1/2基因的变异。新发现的变异丰富了成骨不全症的表现型-基因型数据库,并为这些家系的遗传咨询及产前诊断提供了依据。Objective To analyze the clinical phenotype of six pedigrees affected with osteogenesis imperfecta and their genetic basis.Methods Peripheral blood or abortic tissues of the six pedigrees were collected for the extraction of genomic DNA.Next generation sequencing(NGS)was carried out to detect pathological variants in the genome.Sanger sequencing was used for validating suspected variant among the six pedigrees and 100 healthy controls.Results In pedigree 1,the proband and his daughter both carried a heterozygous c.1976G>C variant of COL1A1.The probands in pedigrees 2 to 6 respectively carried heterozygous variants of c.2224G>A of COL1A2,c.2533G>A of COL1A1,c.2845G>A of COL1A2,c.2532_2540del of COL1A1,and c.1847G>A of COL1A2.The same variants were not detected in their parents and the 100 healthy controls.Conclusion Variants of COL1A1/2 gene probably underlie the pathogenesis for osteogenesis imperfecta in these pedigrees.Discovery of the de novo variants has enriched the spectrum of COL1A1/2 gene variants and facilitated genetic counseling and prenatal diagnosis for the affected pedigrees.

关 键 词：成骨不全症 COL1A1基因 COL1A2基因 基因变异 

分 类 号：R6[医药卫生—外科学]