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.
Department of Otolaryngology and Genetic Testing Center for Deafness, Chinese PLA General Hospital, Beijing, PR China. daipu301@vip.sina.com
Pu
P
Dai
Fei
F
Yu
Bing
B
Han
Xuezhong
X
Liu
Guojian
G
Wang
Qi
Q
Li
Yongyi
Y
Yuan
Xin
X
Liu
Deliang
D
Huang
Dongyang
D
Kang
Xin
X
Zhang
Huijun
H
Yuan
Kun
K
Yao
Jinsheng
J
Hao
Jia
J
He
Yong
Y
He
Youqin
Y
Wang
Qing
Q
Ye
Youjun
Y
Yu
Hongyan
H
Lin
Lijia
L
Liu
Wei
W
Deng
Xiuhui
X
Zhu
Yiwen
Y
You
Jinghong
J
Cui
Nongsheng
N
Hou
Xuehai
X
Xu
Jin
J
Zhang
Liang
L
Tang
Rendong
R
Song
Yongjun
Y
Lin
Shuanzhu
S
Sun
Ruining
R
Zhang
Hao
H
Wu
Yuebing
Y
Ma
Shanxiang
S
Zhu
Bai-Lin
BL
Wu
Dongyi
D
Han
Lee-Jun C
LJ
Wong
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