一对两次发生胎儿骨骼发育异常夫妇的遗传学分析  

Genetic analysis of one couple with a history of fetal skeletal dysplasias twice

作　　者：黎昱 宋婷婷 郑娇 徐盈 李佳 杨红 LI Yu;SONG Tingting;ZHENG Jiao;XU Ying;LI Jia;YANG Hong(Department of Obstetrics and Gynecology,First Affiliated Hospital of Air Force Medical University,Xi’an 710032,China)

机构地区：[1]空军军医大学第一附属医院妇产科,西安710032

出　　处：《山西医科大学学报》2023年第4期550-553,共4页Journal of Shanxi Medical University

基　　金：国家自然科学基金面上项目(82172993)。

摘　　要：目的筛查一对夫妇发生两次胎儿骨骼发育畸形的致病性基因变异。方法在经过遗传咨询,取得知情同意后,利用夫妻外周血及第二次妊娠胎儿样本,提取基因组DNA。应用全外显子测序技术对基因组中外显子及剪切区域进行深度测序分析,对疑似致病变异利用Sanger测序验证候选基因的突变位点。结果胎儿样本携带ALPL c.1120G>A(p.Val374Met)和c.648+1G>A的2个位点突变,为复合杂合突变。其中ALPL c.1120G>A(p.Val374Met)遗传自母亲,c.648+1G>A遗传自父亲,2个突变均为致病突变。结论ALPL基因的复合杂合突变可能是胎儿发育异常的致病原因。对于B超提示骨骼发育异常的胎儿,通过全外显子测序和Sanger测序可以明确致病原因,为夫妻的再生育提供依据。Objective To screen the pathogenic gene mutation in a couple with fetal skeletal dysplasias twice.Methods Genomic DNA was extracted from samples from the second pregnancy fetus and the peripheral blood from the couple after informed consent and genetic counseling.All exons and flanking regions were analyzed by whole exon sequencing.Candidate pathogenic variants in suscepted samples were verified by Sanger sequencing.Results The fetal sample carried compound heterozygous variants c.1120G>A(p.Val374Met)and c.648+1G>A of the ALPL gene.The missense variant,c.1120G>A(P.val374Met),was inherited from the mother,and the other splice site mutation,c.648+1G>A,was inherited from the father.Both of the mutations were reported to be pathogenic.Conclusion The compound heterozygous variants of the ALPL gene may be the cause of the malformation of the fetus.Whole exon sequencing and Sanger sequencing can identify the cause of abnormal bone development and provide evidence for the couple to reproduce.

关 键 词：骨骼发育异常 全外显子测序 ALPL Sanger测序 突变 

分 类 号：R714.5[医药卫生—妇产科学]