甲基丙二酸血症家系的基因诊断与产前诊断  

Mutation analysis and prenatal diagnosis of methylmalonic academia

作　　者：张菁菁[1] 马定远[1] 孙云[1] 洪冬洋 刘刚[1] 王玉国 曾华沙 胡平[1] 许争峰[1] Zhang Jingjing;Ma Dingyuan;Sun Yun(Genetic Medicine Center,Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University (Nangjing Maternity and Child Health Hospital ),Nanjing 210004)

机构地区：[1]南京医科大学附属妇产医院(南京市妇幼保健院)遗传医学中心,南京210004

出　　处：《现代妇产科进展》2022年第7期485-489,共5页Progress in Obstetrics and Gynecology

基　　金：国家自然科学基金(No:82001612)。

摘　　要：目的:通过对35例甲基丙二酸血症家系进行基因检测,明确基因突变类型,并对高风险胎儿进行产前诊断,减少甲基丙二酸血症患儿的出生。方法:应用高通量测序技术检测甲基丙二酸血症相关基因(MUT、MCEE、MMAA、MMAB、MMACHC、MMADHC、LMBRD1、ABCD4、HCFC1、GPHN、PCCA及PCCB),确定家系基因型,并通过Sanger测序对高风险胎儿进行产前诊断。结果:35例甲基丙二酸血症家系中,有30例为MMACHC基因突变导致的cblC型MMA,共检测出12种突变,其中c.79C>T为新变异;5例为MUT基因突变所致的单纯型MMA,共检测出9种突变,其中c.577A>T、c.1591delG、c.1610T>A及c.2216_2219del为新突变。对8个家系的高风险胎儿进行相应突变位点的产前诊断,其中与先证者基因型一致的胎儿,家庭均选择终止妊娠,对野生型和仅携带一个突变位点的胎儿继续妊娠,随访后均发育正常。结论:通过对35例甲基丙二酸血症家系的高通量测序,发现5种新突变,通过基因诊断和产前诊断可有效防止甲基丙二酸血症患儿的出生,并为本地区后续基因筛查、遗传咨询提供依据。Objective:To analyze the gene mutation among 35 families with methylmalonic acidemia(MMA),to determine the mutation spectrum and to conduct the prenatal diagnosis for high-risk fetuses.Method:The next generation sequencing was used to detect the mutations of the genes related to MMA,including MUT,MCEE,MMAA,MMAB,MMACHC,MMADHC,LMBRD1,ABCD4,HCFC1,GPHN,PCCA and PCCB.The Sanger sequencing was performed to determine the gene mutation of high-risk fetuses.Result:There were 12 distinct mutations in MMACHC gene among 30 of 35 families with MMA and 9 mutations in MUT gene among the other 5 families with MMA.Five new mutations were found in the study,including c.79C>T of MMACHC,c.577A>T,c.1591delG,c.1610T>A and c.2216_2219del of MUT gene.Among 8 families with high-risk fetuses,the couples whose fetuses had the same gene mutations with the probands decided to terminate the pregnancy,while the couples with the wild-type or only one mutation fetus would continue the pregnancy.All of them developed normally after follow-up.Conclusion:Five new mutations were found in 35 families with MMA.The mutation analysis and prenatal diagnosis of MMA can avoid the delivery of MMA patients and provide the evidence for gene screening and genetic counseling.

关 键 词：甲基丙二酸血症 MUT MMACHC 突变 产前诊断 

分 类 号：R714.54[医药卫生—妇产科学]