一对常染色体隐性遗传性聋夫妻的遗传学及产前诊断分析  

Genetics and Prenatal Diagnosis Analysis of a Couple with Autosomal Recessive Deafness

作　　者：刘向科 陆祖耀 刘丽娜[1] 郝胜菊[1] 惠玲 张钏[1] 李富萍[1] Liu Xiangke;Lu Zuyao;Liu Lina;Hao Shengju;Hui Ling;Zhang Chuan;Li Fuping(Gansu Provincial Maternity and Child-care Hospital,Lanzhou,730050,China)

机构地区：[1]甘肃省妇幼保健院,兰州730050

出　　处：《听力学及言语疾病杂志》2024年第4期297-301,共5页Journal of Audiology and Speech Pathology

基　　金：国家“十三五”重点专项(2016YFC1000307);国家人口与生殖健康科学数据中心项目(2005DKA32408);国家科技资源共享服务平台计划项目[YCZYPT(2020)05-03];甘肃省科技厅创新基地及人才计划(21JR7RA680);甘肃省科技计划资助项目(22YF7FA094);兰州市科技计划项目(2021-1-182)。

摘　　要：目的对一对常染色体隐性非综合征型聋备孕夫妻患者进行基因分析,以明确其可能的遗传学病因,并为其提供产前诊断。方法应用遗传性听力损失Panel对先证者进行基因分析,应用Sanger测序法对可疑致病位点进行验证,孕妇18周采集羊水后进行产前基因诊断。结果妻子检测到常染色体隐性遗传性聋3型相关基因MYO15A c.10419_10423delCAGCT/c.10294_10308delCCTTGCATCCTTGCC复合杂合变异,分别遗传自其父母。丈夫检测到常染色体隐性遗传性聋77型相关基因LOXHD1 c.6388C>T/exon 33-38 del复合杂合变异,分别遗传自其父母。胎儿羊水检测到母源MYO15A c.10294_10308del CCTTGCATCCTTGCC杂合变异与父源LOXHD1 exon 33-38 del杂合变异,同时还检测到父源CDH23 c.6693delT杂合变异与母源PCDH15 c.5048_5051dupAGAA杂合变异,这两个杂合变异导致胎儿可能患ID/F型Usher综合征。结论该耳聋夫妻为两个不同的耳聋基因变异所致,胎儿患与该夫妻双方相同耳聋的概率很低,但胎儿患二基因突变引起的耳聋的可能性大。对于双方均为耳聋患者的家庭进行产前诊断时应关注二基因突变导致的耳聋。Objective To perform genetic analysis in a family line of a pregnant couple with autosomal recessive non-syndromic deafness in order to identify its possible genetic etiology and provide prenatal diagnosis.Methods Whole-exome sequencing(WES)was used to analyze the genes of the proband,and Sanger sequencing was used to verify the suspected pathogenic loci.Prenatal genetic diagnosis was performed after amniotic fluid collection at 18 weeks of pregnancy.Results Autosomal recessive deafness type 3 related gene MYO15A c.10419_10423delCAGCT/c.10294_10308delCCTTGCATCCTTGCC compound heterozygous variant was found in the wife.A compound heterozygous variant of autosomal recessive deafness type 77-related gene LOXHD1:c.6388C>T/exon 33-38 del.Maternal MYO15A c.10294_10308del CCTTGCATCCTTGCC heterozygous variant were detected in the husband and paternal LOXHD1 exon 33-38 del heterozygous variant were detected in the fetus.At the same time,the paternal CDH23 c.6693delT heterozygous mutation and the maternal PCDH15 c.5048_5051dupAGAA heterozygous mutation were detected in the fetus.These two heterozygous mutations lead to the possibility of the fetus suffering from ID/F Usher syndrome.Conclusion The deafness of the couple is caused by two different deaf gene mutations,and the probability of the fetus having the same deafness as the couple is very low.However,the fetus has a high possibility of having deafness caused by two gene mutations.Therefore,deafness caused by two gene mutations should be paid attention to in the prenatal diagnosis of families with both deaf parents.

关 键 词：MYO15A LOXHD1 CDH23 PCDH15 二基因突变 

分 类 号：R764.431[医药卫生—耳鼻咽喉科]