GJB2 mutation spectrum in 2,063 Chinese patients with nonsyndromic hearing impairment.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Dai
Pu
P
Department of Otolaryngology and Genetic Testing Center for Deafness, Chinese PLA General Hospital, Beijing, PR China. daipu301@vip.sina.com
Yu
Fei
F
Han
Bing
B
Liu
Xuezhong
X
Wang
Guojian
G
Li
Qi
Q
Yuan
Yongyi
Y
Liu
Xin
X
Huang
Deliang
D
Kang
Dongyang
D
Zhang
Xin
X
Yuan
Huijun
H
Yao
Kun
K
Hao
Jinsheng
J
He
Jia
J
He
Yong
Y
Wang
Youqin
Y
Ye
Qing
Q
Yu
Youjun
Y
Lin
Hongyan
H
Liu
Lijia
L
Deng
Wei
W
Zhu
Xiuhui
X
You
Yiwen
Y
Cui
Jinghong
J
Hou
Nongsheng
N
Xu
Xuehai
X
Zhang
Jin
J
Tang
Liang
L
Song
Rendong
R
Lin
Yongjun
Y
Sun
Shuanzhu
S
Zhang
Ruining
R
Wu
Hao
H
Ma
Yuebing
Y
Zhu
Shanxiang
S
Wu
Bai-Lin
BL
Han
Dongyi
D
Wong
Lee-Jun C
LJ
D000465:Algorithms; D044466:Asian People / Q000235:genetics; D002681:China; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005786:Gene Expression Regulation; D006311:Hearing Disorders / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26