Dai Pu, Yu Fei, Han Bing, Liu Xuezhong, Wang Guojian, Li Qi, Yuan Yongyi, Liu Xin, Huang Deliang, Kang Dongyang, Zhang Xin, Yuan Huijun, Yao Kun, Hao Jinsheng, He Jia, He Yong, Wang Youqin, Ye Qing, Yu Youjun, Lin Hongyan, Liu Lijia, Deng Wei, Zhu Xiuhui, You Yiwen, Cui Jinghong, Hou Nongsheng, Xu Xuehai, Zhang Jin, Tang Liang, Song Rendong, Lin Yongjun, Sun Shuanzhu, Zhang Ruining, Wu Hao, Ma Yuebing, Zhu Shanxiang, Wu Bai-Lin, Han Dongyi, Wong Lee-Jun C
Department of Otolaryngology and Genetic Testing Center for Deafness, Chinese PLA General Hospital, Beijing, PR China.
J Transl Med. 2009 Apr 14;7:26. doi: 10.1186/1479-5876-7-26.
Mutations in GJB2 are the most common molecular defects responsible for autosomal recessive nonsyndromic hearing impairment (NSHI). The mutation spectra of this gene vary among different ethnic groups.
In order to understand the spectrum and frequency of GJB2 mutations in the Chinese population, the coding region of the GJB2 gene from 2063 unrelated patients with NSHI was PCR amplified and sequenced.
A total of 23 pathogenic mutations were identified. Among them, five (p.W3X, c.99delT, c.155_c.158delTCTG, c.512_c.513insAACG, and p.Y152X) are novel. Three hundred and seven patients carry two confirmed pathogenic mutations, including 178 homozygotes and 129 compound heterozygotes. One hundred twenty five patients carry only one mutant allele. Thus, GJB2 mutations account for 17.9% of the mutant alleles in 2063 NSHI patients. Overall, 92.6% (684/739) of the pathogenic mutations are frame-shift truncation or nonsense mutations. The four prevalent mutations; c.235delC, c.299_c.300delAT, c.176_c.191del16, and c.35delG, account for 88.0% of all mutantalleles identified. The frequency of GJB2 mutations (alleles) varies from 4% to 30.4% among different regions of China. It also varies among different sub-ethnic groups.
In some regions of China, testing of the three most common mutations can identify at least one GJB2 mutant allele in all patients. In other regions such as Tibet, the three most common mutations account for only 16% the GJB2 mutant alleles. Thus, in this region, sequencing of GJB2 would be recommended. In addition, the etiology of more than 80% of the mutant alleles for NSHI in China remains to be identified. Analysis of other NSHI related genes will be necessary.
GJB2基因的突变是常染色体隐性非综合征性听力损失（NSHI）最常见的分子缺陷。该基因的突变谱在不同种族群体中有所不同。
为了解中国人群中GJB2基因突变的谱型和频率，对2063例非综合征性听力损失患者的GJB2基因编码区进行PCR扩增并测序。
共鉴定出23种致病突变。其中，5种（p.W3X、c.99delT、c.155_c.158delTCTG、c.512_c.513insAACG和p.Y152X）为新发现的突变。307例患者携带两个已确认的致病突变，其中178例为纯合子，129例为复合杂合子。125例患者仅携带一个突变等位基因。因此，GJB2突变占2063例NSHI患者中突变等位基因的17.9%。总体而言，92.6%（684/739）的致病突变是移码截断或无义突变。四种常见突变，即c.235delC、c.299_c.300delAT、c.176_c.191del16和c.35delG，占所有已鉴定突变等位基因的88.0%。GJB2突变（等位基因）的频率在中国不同地区从4%到30.4%不等。在不同的亚种族群体中也有所不同。
在中国的一些地区，检测三种最常见的突变可以在所有患者中鉴定出至少一个GJB2突变等位基因。在其他地区，如西藏，三种最常见的突变仅占GJB2突变等位基因的16%。因此，在该地区，建议对GJB2进行测序。此外，中国超过80%的NSHI突变等位基因的病因仍有待确定。有必要对其他与NSHI相关的基因进行分析。
