一个非综合征MYH9基因新突变家系的遗传学特征及临床表现

Genetic Characteristics and Clinical Manifestation of a New Mutation of the Non-symptomatic MYH9 Gene in a Family

目的对一个非综合征MYH9基因新突变的耳聋家系进行遗传学特征、临床表现及听力学特征分析,为该家系的遗传咨询提供依据。方法对这个耳聋家族成员进行全面的资料搜集,包括基本信息、专科检查、听力学检查、实验室检查、影像学检查等,绘制家系遗传图谱并分析可能存在的遗传方式。同时采集先证者家庭的外周静脉血,结合二代测序、Sanger测序进行检测。结果该耳聋家系可追踪的4代人中耳聋患者为11个,现存患者为8个,遗传方式为常染色体显性遗传。主要参与研究的5人均表现为双侧对称性、渐进性、以高频听力下降为主的迟发性耳聋,发病年龄一般在30岁左右。基因检测结果发现MYH9基因新的基因突变位点c.314A>T:p.Y105F。家系内该变异与耳聋表型共分离,文献未见报道。结论这个非综合征性常染色体显性遗传性耳聋家系的可能致病原因是MYH9 c.314A>T(p.Y105F)的杂合突变,临床主要表现是迟发性耳聋。

Objective Genetic,clinical manifestations and audiological characteristics of a large pedigree with non-symptomatic deafness related to a new MYH9 gene mutation were analyzed to provide basis for genetic consultation.Methods A comprehensive data collection was performed on this family members,including basic information and ENT,audiological,laboratory and imaging examinations.The pedigree was drawn and possible hereditary patterns analyzed.At the same time,peripheral venous blood was collected from the families of the proband,and tested with nextgeneration and Sanger sequencing.Results Eleven persons in this four-generation Chinese family had hearing loss,of whom 8 persons are alive.All affected family members presented with bilateral symmetrical,gradual and late-onset deafness affecting high-frequencies.The age of onset was around 30 years.Except for hearing loss,no lesions were seen in other organs.Genetic testing showed a new c.314A>T(p.Y105F)mutation on the MYH9 gene.This mutation co-segregated with the phenotype in the pedigree,which has not been reported in the literature.Conclusion The pathogenic variation in this non-symptomatic autosomal dominant deafness pedigree is the heterozygous mutation of MYH9 c.314A>T:p.Y105F,and the clinical manifestation is late-onset deafness.