一个患有听力损失和掌跖角化病的中国家庭中GJB2基因的R75Q新发显性突变

R75Q de novo dominant mutation of GJB2 in a Chinese family with hearing loss and palmoplantar keratoderma.

作者信息

Jiang Shu-juan, Di Zheng-hong, Huang Dan, Zhang Jiu-bin, Zhang Yuan-yuan, Li Shu-qin, He Rong

机构信息

Clinical Genetics Department, The Affiliated Shengjing Hospital, China Medical University, 110004 Shenyang, Liaoning, PR China.

Dermatological Department, The Affiliated Shengjing Hospital, China Medical University, 110004 Shenyang, Liaoning, PR China.

出版信息

Int J Pediatr Otorhinolaryngol. 2014 Sep;78(9):1461-6. doi: 10.1016/j.ijporl.2014.06.008. Epub 2014 Jun 16.

DOI:10.1016/j.ijporl.2014.06.008

PMID:24975403

Abstract

OBJECTIVES

Mutations in the GJB2 gene encoding connexin 26 (Cx26) are major causes of hereditary deafness. This study aimed to characterize the mutation profiles of the GJB2 gene in a Chinese family with sensorineural hearing loss.

METHODS

A Chinese family that included three individuals with sensorineural hearing loss and palmoplantar keratoderma underwent complete physical examinations, audiological examinations including pure tone audiometry and auditory brainstem response, skin pathological examination, and temporal CT scans. The entire coding region of GJB2, GJB3, GJB6, and the coding exons (exon7+8 and 19) of SLC26A4, mitochondrial 12SrRNA, and tRNA Ser (UCN) were sequenced. Structural analysis was performed to detect the effects of mutation on the tertiary structure of Cx26.

RESULTS

A dominant GJB2 mutation, c.224G>A (p.Arg75Gln, p.R75Q), was detected in the family. No other mutation was identified in GJB2, GJB3, GJB6, or the coding exons (exon7+8 and 19) of SLC26A4, mitochondrial 12SrRNA, and tRNA Ser (UCN). Structural analysis revealed that the p.R75Q mutation likely affects the structural stability and permeation properties of the Cx26 gap junction channel.

CONCLUSION

Our findings provide further evidence of a correlation between the p.R75Q mutation in Cx26 and a syndromic hearing impairment with palmoplantar keratoderma.

摘要

目的

编码连接蛋白26（Cx26）的GJB2基因的突变是遗传性耳聋的主要原因。本研究旨在明确一个感音神经性听力损失中国家系中GJB2基因的突变谱。

方法

一个包含三名感音神经性听力损失和掌跖角化病患者的中国家系接受了全面的体格检查、听力学检查（包括纯音听力测定和听觉脑干反应）、皮肤病理检查以及颞骨CT扫描。对GJB2、GJB3、GJB6的整个编码区以及SLC26A4、线粒体12SrRNA和tRNA Ser（UCN）的编码外显子（外显子7 + 8和19）进行测序。进行结构分析以检测突变对Cx26三级结构的影响。

结果

在该家系中检测到一个显性GJB2突变，c.224G>A（p.Arg75Gln，p.R75Q）。在GJB2、GJB3、GJB6或SLC26A4、线粒体12SrRNA和tRNA Ser（UCN）的编码外显子（外显子7 + 8和19）中未发现其他突变。结构分析显示，p.R75Q突变可能影响Cx26间隙连接通道的结构稳定性和通透特性。