GJB2 mutation spectrum in 2063 Chinese patients with nonsyndromic hearing impairment

Pu Dai, Fei Yu, Bing Han, Xue Z Liu, Guojian Wang, Qi Li, Yongyi Yuan, Xin Liu, Deliang Huang, Dongyang Kang, Xin Zhang, Huijun Yuan, Kun Yao, Jinsheng Hao, Jia He, Yong He, Youqin Wang, Qing Ye, Youjun Yu, Hongyan LinLijia Liu, Wei Deng, Xiuhui Zhu, Yiwen You, Jinghong Cui, Nongsheng Hou, Xuehai Xu, Jin Zhang, Liang Tang, Rendong Song, Yongjun Lin, Shuanzhu Sun, Ruining Zhang, Hao Wu, Yuebing Ma, Shanxiang Zhu, Bai Lin Wu, Dongyi Han, Lee Jun C Wong

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article number26
JournalJournal of Translational Medicine
Volume7
DOIs
StatePublished - Apr 14 2009

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Audition
Mutation
Alleles
Genes
China
Mutation Rate
Ethnic Groups
Tibet
Frameshift Mutation
Nonsyndromic Deafness
Nonsense Codon
Homozygote
Heterozygote
Defects
Testing
Polymerase Chain Reaction
Population

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

GJB2 mutation spectrum in 2063 Chinese patients with nonsyndromic hearing impairment. / Dai, Pu; Yu, Fei; Han, Bing; Liu, Xue Z; 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.

In: Journal of Translational Medicine, Vol. 7, 26, 14.04.2009.

Research output: Contribution to journalArticle

Dai, P, Yu, F, Han, B, Liu, XZ, Wang, G, Li, Q, Yuan, Y, Liu, X, Huang, D, Kang, D, Zhang, X, Yuan, H, Yao, K, Hao, J, He, J, He, Y, Wang, Y, Ye, Q, Yu, Y, Lin, H, Liu, L, Deng, W, Zhu, X, You, Y, Cui, J, Hou, N, Xu, X, Zhang, J, Tang, L, Song, R, Lin, Y, Sun, S, Zhang, R, Wu, H, Ma, Y, Zhu, S, Wu, BL, Han, D & Wong, LJC 2009, 'GJB2 mutation spectrum in 2063 Chinese patients with nonsyndromic hearing impairment', Journal of Translational Medicine, vol. 7, 26. https://doi.org/10.1186/1479-5876-7-26
Dai, Pu ; Yu, Fei ; Han, Bing ; Liu, Xue Z ; 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. / GJB2 mutation spectrum in 2063 Chinese patients with nonsyndromic hearing impairment. In: Journal of Translational Medicine. 2009 ; Vol. 7.
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title = "GJB2 mutation spectrum in 2063 Chinese patients with nonsyndromic hearing impairment",
abstract = "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.",
author = "Pu Dai and Fei Yu and Bing Han and Liu, {Xue Z} and Guojian Wang and Qi Li and Yongyi Yuan and Xin Liu and Deliang Huang and Dongyang Kang and Xin Zhang and Huijun Yuan and Kun Yao and Jinsheng Hao and Jia He and Yong He and Youqin Wang and Qing Ye and Youjun Yu and Hongyan Lin and Lijia Liu and Wei Deng and Xiuhui Zhu and Yiwen You and Jinghong Cui and Nongsheng Hou and Xuehai Xu and Jin Zhang and Liang Tang and Rendong Song and Yongjun Lin and Shuanzhu Sun and Ruining Zhang and Hao Wu and Yuebing Ma and Shanxiang Zhu and Wu, {Bai Lin} and Dongyi Han and Wong, {Lee Jun C}",
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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, Xue Z

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

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.

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