摘要
目的对一个常染色体隐性遗传的先天性耳聋核心家系进行遗传学分析,探究该家系的致病基因。方法对该耳聋家系成员进行病史采集、体格检查及听力学检查,分析家系的遗传特征并绘制家系图,通过高通量测序对先证者进行耳聋基因筛查,使用Sanger测序在家系中对可疑致病位点进行共分离分析。结果该家系2代4人,1例耳聋患者,为常染色体隐性遗传;高通量测序发现先证者MYO7A基因存在NM_000260.3:c.765C>A(p.F255L)和c.275_278dupACCT(p.I94fs)两个新的突变位点,依据ACMG变异分类指南判定为可疑致病性和致病性变异;经Sanger测序验证c.765C>A突变来自父亲,c.275_278dupACCT突变来自于母亲,姐姐携带c.765C>A突变,变异在家系中与表型共分离。结论MYO7A基因新的复合杂合突变c.765C>A和c.275_278dupACCT与上述常染色体隐性遗传性耳聋密切相关,丰富了MYO7A基因突变谱,为遗传性耳聋的遗传咨询提供依据。
Objective To analyze the causative mutation of a nuclear family with autosomal recessive congenital hearing loss. Methods Medical history collection, detailed physical examination and hearing test were performed on the family members. High throughput sequencing was conducted for screening of hearing loss genes. Suspected mutations were analyzed by Sanger sequencing. Results There were 4 people of 2 generations in this family, one member with hearing loss. High throughput sequencing and Sanger sequencing revealed the proband carrying compound heterozygous mutation of MYO7 A, NM_000260.3:c.765 C>A(p.F255 L) from her father and c.275_278 dupACCT(p.I94 fs) from her mother, and her sister carried the c.765 C>A mutation. According to the standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, c.765 C>A was classified as likely pathogenic and c.275_278 dupACCT classified as pathogenic. Conclusion Novel compound heterozygous mutation of MYO7A is identified as the causative mutation for congenital hearing loss in this family, which enriches the mutation spectrum of MYO7A and provides a basis for genetic counseling of hereditary hearing loss.
作者
李萌
孙金仓健
刘敏
文卫平
LI Meng;SUNJIN Cangjian;LIU Min;WEN Weiping(Department of Otolaryngology,Otorhinolaryngology Institute,the First Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080,China;Department of Otolaryngology,the Sixth Affiliated Hospital of Sun Yat-sen University,Guangzhou 510655,China)
出处
《中国耳鼻咽喉颅底外科杂志》
CAS
2022年第3期36-40,共5页
Chinese Journal of Otorhinolaryngology-skull Base Surgery
基金
中国博士后科学基金第68批面上资助二等(2020M683099)。
关键词
遗传性耳聋
高通量测序
MYO7A基因
突变分析
Hereditary hearing loss
High throughput sequencing
MYO7A gene
Mutation analysis
