TY - JOUR
T1 - GJB2 mutation spectrum in 2063 Chinese patients with nonsyndromic hearing impairment
AU - Dai, Pu
AU - Yu, Fei
AU - Han, Bing
AU - Liu, Xuezhong
AU - Wang, Guojian
AU - Li, Qi
AU - Yuan, Yongyi
AU - Liu, Xin
AU - Huang, Deliang
AU - Kang, Dongyang
AU - Zhang, Xin
AU - Yuan, Huijun
AU - Yao, Kun
AU - Hao, Jinsheng
AU - He, Jia
AU - He, Yong
AU - Wang, Youqin
AU - Ye, Qing
AU - Yu, Youjun
AU - Lin, Hongyan
AU - Liu, Lijia
AU - Deng, Wei
AU - Zhu, Xiuhui
AU - You, Yiwen
AU - Cui, Jinghong
AU - Hou, Nongsheng
AU - Xu, Xuehai
AU - Zhang, Jin
AU - Tang, Liang
AU - Song, Rendong
AU - Lin, Yongjun
AU - Sun, Shuanzhu
AU - Zhang, Ruining
AU - Wu, Hao
AU - Ma, Yuebing
AU - Zhu, Shanxiang
AU - Wu, Bai Lin
AU - Han, Dongyi
AU - Wong, Lee Jun C.
N1 - Funding Information:
The authors also would like to thank the Fuyang School for the Deaf and Dumb (Anhui province), Beijing No.3 School for the Deaf (Beijing), Pinggu Special Education School (Beijing), Beijing Children's Hospital(Beijing), Fuzhou Special Education School (Fujian province), Lanzhou Convalescent Center for Deaf Children (Gansu province), Gansu Convalescent Ccenter for Deaf Children (Gansu province), Foshan School for the Deaf and Dumb (Guangdong province), Liuzhou School for the Bblind Deaf and Dumb (Guangxi province), Guiyang School for the Blind, Deaf and Dumb (Guizhou Province), Zhuozhou and Gaobeidian School for the Ddeaf and Dumb (Hebei province), Mudanjiang Special Education School (Heilongjiang province), Anyang Special Education School (Henan province), Wuhan Yimeng Convalescent Center for Deaf Children (Hubei province), Chifeng Special Education School (Inner Mongolia), Nantong School for the Deaf and Dumb (Jiangsu province), Haian School for the Deaf and Dumb (Jiangsu province), Haimen School for the Deaf and Dumb (Jiangsu province), Rugao School for the Deaf and Dumb (Jiangsu province), Tongzhou School for the Deaf and Dumb (Jiangsu province), Jilin Special Education School (Jilin province), Yin-chuan School for the Blind, Deaf and Dumb (Ningxia Province), Xining Special Education School (Qinghai province), Changan School for the Deaf and Dumb (Shaanxi province), Affiliated Pediatric Medical Center of Shanghai Jiao Tong University (Shanghai), Yuncheng School for the Deaf and Dumb (Shanxi province), Yuncheng Disabled Person's Federation (Shanxi province), Yuncheng Convalescent Center for Deaf Children (Shanxi province), Chengdu Special Education School (Sichuan province), Urumchi School for the Deaf and Dumb (Xinjiang province), Korla School for the Deaf and Dumb (Xinjiang province), Kunming Huaxia Secondary School (Yunnan province), Kunming Convalescent Center for Deaf Children (Yunnan province), Lincang Special Education School (Yunnan province), Kunming Convalescent Center for Deaf Children (Yunnan province) and Lhasa Special Education School (Tibet municipality area) for their fundamental support and contributions to this work.
Funding Information:
The authors would like to thank Dr. Dennis Johnson and Dr. Raye L. Alford for their valuable suggestions. This work was supported by the Chinese National Nature Science Foundation Research Grant 30728030,30872862, and Chinese Capital Medical Development Scientific Funding 2005-1032 to Dongyi Han.
PY - 2009/4/14
Y1 - 2009/4/14
N2 - 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. Conclusion: 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.
AB - 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. Conclusion: 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.
UR - http://www.scopus.com/inward/record.url?scp=65649116240&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=65649116240&partnerID=8YFLogxK
U2 - 10.1186/1479-5876-7-26
DO - 10.1186/1479-5876-7-26
M3 - Article
C2 - 19366456
AN - SCOPUS:65649116240
VL - 7
JO - Journal of Translational Medicine
JF - Journal of Translational Medicine
SN - 1479-5876
M1 - 26
ER -