Jiang Hua, Chen Jia, Shan Xin-Ji, Li Ying, He Jian-Guo, Yang Bei-Bei
Department of Otolaryngology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
Mol Med Rep. 2014 Jul;10(1):379-86. doi: 10.3892/mmr.2014.2148. Epub 2014 Apr 15.
The frequency and distribution of genetic mutations that cause deafness differ significantly according to ethnic group and region. Zhejiang is a province in the southeast of China, with an exceptional racial composition of the population caused by mass migration in ancient China. The purpose of the present study was to investigate the prevalence and spectrum of gap junction‑β2 (GJB2), solute carrier family 26 (anion exchanger) member 4 (SLC26A4) and GJB3 mutations in patients with autosomal recessive non‑syndromic hearing loss (ARNHL) in this area. A total of 176 unrelated pediatric patients with ARNHL were enrolled in the study. A genomic DNA sample was extracted from the peripheral blood. Polymerase chain reaction was employed, and the products were sequenced to screen for mutations in GJB2. In addition, a SNaPshot sequencing method was utilized to detect four hotspot mutations in SLC26A4 (IVS7‑2A>G and c.2168A>G) and GJB3 (c.538C>T and c.547G>A). All patients were subjected to a temporal bone computed tomography scan to identify enlarged vestibular aqueducts (EVA). In total, 14 different mutations, including two new mutations (p.W44L and p.D66N) of GJB2, were detected. The most common pathogenic mutation of GJB2 was c.235delC (15.1%), followed by c.176_191del16 (1.7%), c.299_300delAT (1.7%), c.508_511dup (0.85%) and c.35delG (0.28%) of the total alleles. Mutation analysis of SLC26A4 demonstrated that 13.6% (24/176) of patients carried at least one mutant allele. The patients with EVA (84.2%) had SLC26A4 mutations, and 31% had homozygous mutations. Only one patient carried a heterozygous mutation of GJB3 (c.538C>T). Compared with the other regions of China, in the present population cohort, the prevalence and spectrum of mutations in GJB2 was unique, and in patients with EVA the frequency of a homozygous mutation in SLC26A4 was significantly lower. These findings may be of benefit in genetic counseling and risk assessment for families from this area of China.
导致耳聋的基因突变的频率和分布因种族和地区的不同而有显著差异。浙江是中国东南部的一个省份，由于古代大规模的人口迁移，其人口种族构成独特。本研究旨在调查该地区常染色体隐性非综合征性听力损失（ARNHL）患者中缝隙连接蛋白β2（GJB2）、溶质载体家族26（阴离子交换器）成员4（SLC26A4）和GJB3基因突变的发生率及突变谱。共有176例无关的ARNHL儿科患者纳入本研究。从外周血中提取基因组DNA样本。采用聚合酶链反应，并对产物进行测序以筛查GJB2中的突变。此外，利用SNaPshot测序法检测SLC26A4（IVS7-2A>G和c.2168A>G）和GJB3（c.538C>T和c.547G>A）中的四个热点突变。所有患者均接受颞骨计算机断层扫描以确定是否存在前庭导水管扩大（EVA）。总共检测到14种不同的突变，包括GJB2的两个新突变（p.W44L和p.D66N）。GJB2最常见的致病突变是c.235delC（15.1%），其次是c.176_191del16（1.7%）、c.299_300delAT（1.7%）、c.508_511dup（0.85%）和c.35delG（0.28%）（占总等位基因）。SLC26A4的突变分析表明，13.6%（24/176）的患者携带至少一个突变等位基因。患有EVA的患者中84.2%有SLC26A4突变，31%为纯合突变。只有1例患者携带GJB3的杂合突变（c.538C>T）。与中国其他地区相比，在本研究人群队列中，GJB2突变的发生率和突变谱是独特的，并且在患有EVA的患者中，SLC26A4纯合突变的频率显著更低。这些发现可能有助于对来自中国该地区的家庭进行遗传咨询和风险评估。
