WFS1基因突变致一个遗传性耳聋家系的临床表型及基因型分析

Clinical Phenotype and Genotype Analysis of a Family with Inherited Deafness Caused by WFS1 Gene Mutation

目的分析一个遗传性耳聋家系的临床特征及致病基因,总结该致病位点的临床表型及特点,为该家系遗传咨询提供依据。方法对该家系成员进行详细病史询问、体格检查,完善相关听力学及影像学检查;抽取部分家系成员的外周静脉血,利用已知耳聋基因目标区域高通量测序技术和Sanger测序验证,进行耳聋致病基因的鉴定与分析。结果该家系临床均表现为极重度非综合征型感音神经性语前聋,经检测发现该家系中先证者及其母亲、弟、妹均携带WFS1基因c.2051C>T(p.A684V)杂合突变,Sanger测序验证该基因突变基因型和听力表型共分离,符合常染色体显性遗传特征。结论WFS1基因c.2051C>T(p.A684V)杂合突变为该家系耳聋致病原因,进一步验证了c.2051C>T突变可能为WFS1基因在中国人群中的热点突变,不同于欧美人群,该致病突变在中国人群中主要临床表型为语前非综合征型感音神经性聋。

Objective To analyze the clinical characteristics and pathogenic genes of a family with hereditary deafness and summarize the clinical characteristics of the pathogenic gene.Methods A detailed medical history inquiry,physical examination,and related audiology and imaging examinations were performed on the family members;the peripheral venous blood of some family members was collected,and the high-throughput sequencing technology and Sanger sequencing of known deaf gene target regions were used for verification.The families of the witnesses conduct the identification and analysis of the genes causing deafness.Results The family was clinically manifested as prelingual non-syndromic sensorineural hearing loss(profound).The genealogical analysis was consistent with autosomal dominant inheritance characteristics.Next generation sequencing found that the proband and his mother,younger brother,and sister in the family were WFS1:NM_006005.3:c.2051C>T(p.A684V)heterozygous mutations.Sanger sequencing verified that this gene mutation is consistent with hearing phenotype and genotype cosegregation.Conclusion The WFS1 gene c.2051C>T(p.A684V)heterozygous mutation is the gene that causes deafness in this family.The results further verify that the c.2051C>T mutation may be a hot spot mutation of WFS1 gene in Chinese population.Unlike European and American populations,the main clinical phenotype of this pathogenic mutation in the Chinese population is prelingual non-syndromic sensorineural hearing loss.