一个常染色体显性遗传非综合征性耳聋家系的HBSY-012家系基因检测及遗传学特征分析  

Gene detection and genetic analysis of HBSY-012 in a family with autosomal dominant nonsyndromic deafness

作　　者：马静 雷培良 李云[1] MA Jing;LEI Peiliang;LI Yun(Ophthalmology and Otorhinolaryngology,Shijiazhuang Third Hospital,Shijiazhuang,Hebei 050000,China)

机构地区：[1]石家庄市第三医院五官科,河北石家庄050000

出　　处：《中国优生与遗传杂志》2023年第10期2158-2161,共4页Chinese Journal of Birth Health & Heredity

摘　　要：目的 研究常染色体显性遗传非综合征性耳聋家系的HBSY-012家系致病基因的突变位点,分析基因型与异常表型的关系。方法 采集一个常染色体显性遗传性非综合征型耳聋HBSY-012家系患者的临床资料,分析耳聋表型、遗传方式,并绘制家系图。提取家系成员外周血DNA,利用耳聋相关基因靶向测序,对家系成员进行全基因组外显子测序,寻找致病基因,采用Sanger测序技术验证突变位点。结果 HBSY-012家系现存四代共19人,9人诊断为感音神经性聋,耳聋表型特点为语后聋,发病早期呈现高频感音神经性耳聋,双耳对称,随着疾病进展出现渐进性听力下降,且快速下降,并转变成全频受累的极重度感音神经性耳聋。该家系的9例患者均在5~7岁开始出现听力下降,患者中年龄最大68岁,最小10岁。HBSY-012家系系谱分析该家系符合常染色体显性遗传特征。遗传性耳聋基因筛查检测显示EVI5基因NM_005665:c.2399C>T变异、ANKMY2基因NM_020319:c.822_826del变异以及CCDC50基因c.363C>T(p.Leu121Phe)杂合突变,其中CCDC50基因c.363C>T(p.Leu121Phe)杂合突变源自父方,属于致病突变。结论 本研究从一个常染色体显性遗传非综合征性耳聋家系的HBSY-012家系中发现携带的致病基因及突变位点:CCDC50基因c.363C>T(p.Leu121Phe)杂合突变,该突变导致该家系成员非综合征性耳聋。Objective To study the mutation site of pathogenic gene in HBSY-012 family of autosomal dominant non-syndromic deafness,and to analyze the relationship between genotype and abnormal phenotype.Methods The clinical data of an autosomal dominant non-syndromic deafness HBSY-012 family were collected to analyze the phenotype and genetic pattern of deafness,and the family map was drawn.The peripheral blood DNA of family members was extracted,and the whole genome exome sequencing was performed on family members by targeted sequencing of deafness-related genes,looking for pathogenic genes,and Sanger sequencing technology was used to verify the mutation site.Results HBSY-012 family has a total of 19 people in four generations,9 of whom were diagnosed with sensorineural deafness,the phenotype of deafness was characterized by posterior deafness,high-frequency sensorineural deafness in the early stage of the disease,symmetrical in both ears,progressive hearing loss with the progression of the disease,and rapid decline,and transformation into extremely severe sensorineural hearing loss with full-frequency involvement.All 9 patients in this family began to have hearing loss at the age of 5~7,and the oldest was 68 years old and the youngest was 10 years old.HBSY-012 lineage analysis showed that the family line conformed to autosomal dominant characteristics.Hereditary deafness gene screening tests showed that EVI5 gene NM_005665:c.2399C>T variant,ANKMY2 gene NM_020319:c.822_826del variant and CCDC50 gene c.363C>T(p.Leu121Phe)heterozygous mutation,among which the CCDC50 gene c.363C>T(p.Leu121Phe)heterozygous mutation mutation originated from the father and was a pathogenic mutation.Conclusion In this study,a heterozygous mutation of the CCDC50 gene c.363C>T(p.Leu121Phe)was found in the HBSY-012 family of an autosomal dominant nonsyndromic deafness family,which caused nonsyndromic deafness in members of this family.

关 键 词：常染色体显性遗传 致病基因 突变位点 耳聋 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]