戊二酸血症ⅡC型胎儿1例的临床表型及遗传学分析  

Clinical phenotype and genetic analysis of a fetus with Glutaracidemia typeⅡC

作　　者：翟闪闪[1] 刘灵[1] 袁莉敏[1] 程国梅[1] Zhai Shanshan;Liu Ling;Yuan Limin;Cheng Guomei(Prenatal Diagnosis Center,the Third Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)

机构地区：[1]郑州大学第三附属医院产前诊断中心,郑州450052

出　　处：《中华医学遗传学杂志》2023年第6期718-722,共5页Chinese Journal of Medical Genetics

基　　金：河南省科技发展计划(202102310471)。

摘　　要：目的探讨1例戊二酸血症ⅡC型(GAⅡC)胎儿的临床表型及基因变异特征。方法选取2021年12月因"孕17周胎儿超声提示双肾体积增大并回声增强、羊水少"来郑州大学第三附属医院产前诊断中心就诊的1例32岁孕妇及其GAⅡC胎儿作为研究对象,收集孕妇的相关临床资料及胎儿的影像学检查信息。采集孕妇的羊水标本及孕妇夫妇的外周静脉血样本进行家系全外显子组测序,对候选变异进行Sanger测序家系验证,并利用低深度全基因组测序技术检测拷贝数变异(CNV)。结果胎儿孕18周超声提示双肾体积增大并回声增强、肾实质内裂隙样管状无回声、羊水过少。孕22周MRI提示双肾体积增大、T2信号异常均匀增高并DWI信号降低、双肺体积小并T2信号呈稍高信号。CNV检测结果未见异常。测序分析提示胎儿ETFDH基因存在母源性c.1285+1G>A及父源性c.343_344delTC复合杂合变异。根据美国医学遗传学与基因组学学会相关指南,判定二者均为致病变异(PVS1+PM2_Supporting+PS3_Supporting;PVS1+PM2_Supporting+PM3)。结论ETFDH基因c.1285+1G>A和c.343_344delTC复合杂合变异可能是患儿的遗传学病因,GAⅡC在胎儿期可表现为双侧肾脏体积增大并回声增强、羊水过少。上述发现丰富了ETFDH基因的变异谱。Objective To explore the clinical phenotype and genetic variants of a fetus with Glutaracidemia typeⅡC(GAⅡC).Methods Clinical data of a 32-year-old pregnant woman and her fetus with GAⅡC diagnosed at the Third Affiliated Hospital of Zhengzhou University in December 2021 due to the enlargement and enhanced echo of the kidneys and oligohydramnios fluid at 17 weeks were analyzed retrospectively.Amniotic fluid sample of the fetus and peripheral blood samples of the couple were collected for whole exome sequencing(WES).Candidate variants were verified by Sanger sequencing.Copy number variation(CNV)was detected by using low-coverage whole genome sequencing(CNV-seq).Results At 18 weeks′gestation,ultrasound revealed that the fetus had enlargement and enhanced echo of the kidneys along with no echo of renal parenchymal tubular fissure and oligohydramnios.MRI at 22 weeks′gestation confirmed that both kidneys were enlarged with uniformly increased abnormal T2 signal and decreased DWI signal.The volume of both lungs was small,with slightly higher T2 signal.No CNV was detected in the fetus.WES revealed that the fetus has harbored compound heterozygous variants of the ETFDH gene,namely c.1285+1G>A and c.343_344delTC,which were inherited from its father and mother,respectively.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),both variants were classified as pathogenic(PVS1+PM2_Supporting+PS3_Supporting;PVS1+PM2_Supporting+PM3).Conclusion The c.1285+1G>A and c.343_344delTC compound heterozygous variants of the ETFDH gene probably underlay the disease in this fetus.TypeⅡC glutaric acidemia may manifest as bilateral kidney enlargement with enhanced echo and oligohydramnios.Discovery of the c.343_344delTC has enriched the spectrum of ETFDH gene variants.

关 键 词：多酰基辅酶A脱氢酶缺乏 戊二酸血症ⅡC型 ETFDH基因 全外显子组测序 孕妇 胎儿 

分 类 号：R714.5[医药卫生—妇产科学]