Huang Aiping, Yuan Yongyi, Duan Naichao, Jiang Xinxia, Wang Baoshan, Liu Yanping, Kang Dongyang, Zhang Xin, Zhu Qingwen, Dai Pu
Department of Otolaryngology, Head & Neck Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050018, Hebei, China; Department of Otolaryngology, Head & Neck Surgery, Chinese PLA General Hospital, Beijing 100853, China.
Department of Otolaryngology, Head & Neck Surgery, Chinese PLA General Hospital, Beijing 100853, China.
Int J Pediatr Otorhinolaryngol. 2014 Apr;78(4):599-603. doi: 10.1016/j.ijporl.2014.01.008. Epub 2014 Jan 17.
To assess the molecular etiology of nonsyndromic sensorineural hearing loss (NSHL) in members of an affected Chinese family.
Common hearing-related genes including gap junction beta 2 (GJB2), SLC26A4, mitochondrial DNA 12S rRNA, GJB3 and GJB6 were examined in a family consisting of a normal hearing father, an NSHL-affected mother, one normal-hearing child and three NSHL-affected children. Specific primers were used in polymerase chain reactions to amplify the coding regions of the above genes from the peripheral blood DNA from each family member, and the genes were analyzed by direct sequencing. The subjects were evaluated for phenotypic characterization using audiometric testing and radiological examination of the inner ear.
Pathogenic mutations in the GJB2 gene were identified. The affected mother showed a heterozygous G→A transition at nucleotide 232, resulting in an alanine to threonine substitution at codon 78 (p.A78T), and the normal hearing father had a c.35insG insertion mutation. The three affected children displayed heterozygosity for the GJB2 mutations, showing a previously unreported combination of c.35insG and c.232G>A.
The GJB2 mutations account for a significant proportion of NSHL in affected individuals worldwide. Genetic and audiological data analysis of a Chinese family with NSHL revealed a novel c.35insG/c.232G>A compound heterozygous state. Our results highlight the complexity of the GJB2 genotypes and phenotypes.
评估一个受影响的中国家庭中成员非综合征性感音神经性听力损失（NSHL）的分子病因。
在一个由听力正常的父亲、患NSHL的母亲、一个听力正常的孩子和三个患NSHL的孩子组成的家庭中，检测包括缝隙连接蛋白β2（GJB2）、SLC26A4、线粒体DNA 12S rRNA、GJB3和GJB6在内的常见听力相关基因。使用特异性引物通过聚合酶链反应从每个家庭成员的外周血DNA中扩增上述基因的编码区，并通过直接测序分析这些基因。使用听力测试和内耳影像学检查对受试者进行表型特征评估。
在GJB2基因中鉴定出致病突变。受影响的母亲在核苷酸232处显示G→A转换，导致密码子78处丙氨酸被苏氨酸取代（p.A78T），听力正常的父亲有一个c.35insG插入突变。三个受影响的孩子显示出GJB2突变的杂合性，表现出一种以前未报道的c.35insG和c.232G>A的组合。
GJB2突变在全球受影响个体的NSHL中占很大比例。对一个患NSHL的中国家庭进行的遗传和听力学数据分析揭示了一种新的c.35insG/c.232G>A复合杂合状态。我们的结果突出了GJB2基因型和表型的复杂性。
