1例ACTA1基因突变导致先天性肌病胎儿的超声检查及遗传学分析  

Ultrasound examination and genetic analysis of a fetus with congenital myopathy caused by ACTA1 gene mutation

作　　者：王颖 章静慧 范丽红 楼小花 邵慧芬 沈学萍 沈国松 WANG Ying;ZHANG Jinghui;FAN Lihong;LOU Xiaohua;SHAO Huifen;SHEN Xueping;SHEN Guosong(Huzhou Maternity&Child Health Care Hospital,Huzhou,Zhejiang 313000,China)

机构地区：[1]湖州市妇幼保健院,浙江湖州313000

出　　处：《中国优生与遗传杂志》2024年第8期1673-1676,共4页Chinese Journal of Birth Health & Heredity

基　　金：湖州市公益性应用研究项目(2021GZ70)。

摘　　要：目的探讨1例四肢姿势异常胎儿的遗传学病因,并进行遗传咨询以及再生育指导。方法选取1个初次妊娠胎儿超声提示四肢姿势异常的家系作为研究对象,收集临床信息,行羊膜腔穿刺,对该家系进行全外显子组测序分析以及Sanger测序验证,用在线生物信息软件对变异位点进行致病性预测以及对应氨基酸的保守性分析。结果超声提示胎儿胸腔积液伴颈背部皮肤软组织增厚,胎儿上下肢姿势较固定;家系全外显子组测序发现胎儿存在ACTA1基因新发杂合变异c.355G>A(p.Glu119Lys),功能预测软件对该变异的预测结果偏向于致病性变异,且该变异在多个数据库中均未见收录,既往研究显示ACTA1突变可导致先天性肌病。根据美国医学遗传学与基因组学学会相关指南,该变异为可能致病性变异(PP3_Strong+PP2+PS2_Supporting+PM2_Supporting+PM5_Supporting)。结论家系全外显子组测序为该异常胎儿找到了遗传学病因,为该家庭的遗传咨询提供了依据。另外,该研究通过发现新的变异位点拓展了ACTA1的突变谱,并且很好地描述了ACTA1相关肌病的宫内表型。Objective To investigate the genetic etiology of a fetus with abnormal posture of limbs,and to provide theoretical basis for genetic counseling and fertility guidance.Methods A family with abnormal fetal ultrasound during the first pregnancy was selected as the research object.We collected the clinical information,then performed amniocentesis,whole exome sequencing analysis,and Sanger sequencing.Online biological information software was used to predict the pathogenicity of the variant and to analyze the conservation of the corresponding amino acid.Results Prenatal ultrasound showed fetal pleural effusion,thickened nuchal fold,and fixed posture of the limbs.Trio-whole exome sequencing revealed that the fetus carried a de novel heterozygous variant of ACTA1 gene:c.355G>A(p.Glu119Lys).Software prediction showed that the variant tended to be pathogenic and was not included in the common databases.Previous studies showed that ACTA1 mutation could lead to congenital myopathy.According to the American College of Medical Genetics and Genomics guidelines,the variant c.355G>A was classified as likely pathogenic(PP3_Strong+PP2+PS2_Supporting+PM2_Supporting+PM5_Supporting).Conclusion The whole exome sequencing identified the genetic cause of the abnormal fetus,and provided a basis for genetic counseling.In addition,this study expanded the mutant spectrum of ACTA1 by identifying a novel variant and well described the intrauterine phenotype of ACTA1-associated myopathy.

关 键 词：姿势异常 ACTA1基因 先天性肌病 遗传咨询 

分 类 号：R714.5[医药卫生—妇产科学] R445.1[医药卫生—临床医学]