一个WFS1基因复合杂合变异所致Wolfram综合征1型耳聋家系的遗传学诊断  

Genetic and prenatal diagnosis of a Chinese pedigree with autosomal recessive Wolfram syndrome 1 due to compound heterozygous variants of WFS1 gene

作　　者：亢鸿飞[1] 杨凯[1] 孔祥东[1] Kang Hongfei;Yang Kai;Kong Xiangdong(Genetics and Prenatal Diagnosis Center,Department of Obstetrics and Gynecology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)

机构地区：[1]郑州大学第一附属医院妇产科遗传与产前诊断中心,郑州450052

出　　处：《中华医学遗传学杂志》2022年第7期698-702,共5页Chinese Journal of Medical Genetics

基　　金：国家重点研发计划(2018YFC1002206-2)。

摘　　要：目的探究一个综合征型耳聋家系的致病基因变异类型,明确可能的遗传学病因。方法应用高通量测序技术对一个综合征型耳聋家系中的先证者(听力下降合并视神经萎缩和高血糖)进行415个遗传性耳聋相关基因的序列检测,使用Sanger测序法对高通量测序结果进行验证,并对先证者父母和胎儿进行检测。结果先证者基因组DNA中检测到2个与Wolfram综合征1型耳聋相关的WFS1基因c.2389G>A(p.Asp797Asn)(已知致病)杂合变异和c.2345C>T(p.Pro782Leu)(疑似致病,PM2+PM3+PP1+PP3+PP4,尚未见报道)杂合变异,先证者父母听力正常,分别为WFS1基因c.2389G>A杂合变异和c.2345C>T杂合变异携带者。胎儿携带WFS1基因复合杂合变异,发展为与先证者同样的综合征型耳聋患者的可能性大。结论该家系为一个罕见的Wolfram综合征1型耳聋家系,WFS1基因复合杂合变异是该家系耳聋发生的遗传学病因,可以根据WFS1基因的两个变异对家系进行遗传咨询和产前诊断。Objective To explore the genetic pathogenicity for a Chinese pedigree affected with severe syndromic deafness.Methods High-throughput sequencing was carried out to analyze the 415 genes associated with hereditary deafness in the proband who has hearing loss in association with optic atrophy and hyperglycemia.Candidate variants were verified by Sanger sequencing of the proband,her parents and the fetus.Results The proband was found to harbor compound heterozygous variants of WFS1 gene,namely c.2389G>A(p.Asp797Asn)and c.2345C>T(p.Pro782Leu),which was known to underlie Wolfram syndrome 1.The proband′s parents had normal hearing and were both heterozygous carriers for the above variants.The fetus was found to harbor the same compound heterozygous variants and was predicted to have a high risk.Conclusion The compound heterozygous variants of c.2389G>A and c.2345C>T of the WFS1 gene probably underlay the pathogenesis of hearing loss in the proband.Above finding has facilitated genetic counseling and prenatal diagnosis for this family.

关 键 词：WFS1基因 Wolfram综合征1型 耳聋 基因诊断 产前诊断 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]