摘要
目的分析4个成骨不全家系致病基因COL1A1、COL1A2基因致病突变位点，为家系遗传咨询和产前诊断提供依据。方法应用二代测序对4个成骨不全家系的先证者COL1A1、COL1A2基因编码区进行外显子检测，获得变异序列后，针对所检出变异序列经PCR扩增后进行Sanger双向测序，对4个成骨不全家系中4例先证者及其家系成员和200名正常个体的COL1A1、COL1A2基因序列进行变异验证分析，确定致病突变后，对1个家系中的高危胎儿进行产前诊断。结果家系1和2先证者分别携带COL1A1基因C．760G〉A（P．Gly254Arg）、C．608G〉T（P．Gly203Val）杂合突变，父母均未携带该突变；家系3先证者和先证者女儿均携带COL1A1基因c．299-1G〉C杂合突变，先证者妻子未携带该突变；产前诊断结果显示家系3胎儿未携带与先证者相同的突变，与B超影像结果一致。家系4先证者携带C0L1A2基因c．1990G〉C（p．Gly664Arg）杂合突变，父母均未携带该突变；200名正常个体未检测到上述突变。其中COL1A1基因C．299-1G〉C和COLJA2基因C．1990G〉C（p．Gly664Arg）突变为未报道过的新突变。结论COL1A1、COL1A2基因突变是这4个成骨不全家系的致病原因，本研究结果丰富了COL1A1、COL1A2基因突变谱，为家系的遗传咨询和产前诊断提供了依据。
Objective To detect potential mutations of COLIA1 and COLIA2 genes in four Chinese pedigrees affected with osteogenesis imperfecta （OI） and provide prenatal diagnosis for a fetus at 18th gestational week. Methods All coding regions and exon/intron boundaries of the COL1A1 and COL1A2 genes were analyzed with targeted next-generation sequencing （NGS）. Suspected mutations were confirmed with Sanger sequencing in the probands, unaffected relatives and 200 unrelated healthy individuals. Prenatal diagnosis for a high-risk fetus was carried out through Sanger sequencing. Results The probands of families 1 and 2 have respectively carried a e. 760G〉A （p. Gly254Arg） and a c. 608G〉T （p. Gly203Val） mutation of the COL1A1 gene. For family 3, the proband and his daughter have carried a novel c. 299-1G〉 C splicing mutation of the COLIA1 gene. The same mutation was not found in the fetus of this family. For family 4, the prohand has carried a novel e. 1990G〉C （p. Gly664Arg） mutation of the COL1A2 gene. The four mutations were not found in the unaffected relatives and 200 unrelated healthy individuals. Conclusion The mutations of the COL1A1 and COL1A2 genes probably underlie the disease in the four families. NGS combined with Sanger sequencing can provide an effective and accurate method for their genetic and prenatal diagnosis.
作者
白莹
孔祥东
刘宁
任淑敏
郭宏湘
赵凯慧
Bai Ying Kong Xiangdong Liu Ning Ren Shumin Guo Hongxiang Zhao Kaihui(Center of Prenatal Diagnosis Department of Pediatrics （Guo HX）, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China)
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2017年第5期705-708,共4页
Chinese Journal of Medical Genetics
基金
国家自然科学基金青年科学基金项目（81501851）
2016年度河南省产学研合作项目（162107000017）
河南省医学科技攻关计划项目（201702003）
