A six-generation Chinese family in haplogroup B4C1C exhibits high penetrance of 1555A > G-induced hearing Loss

BMC Medical Genetics

Research Article

Zhengmin Wang¹  Ning Cong¹  Guoling Chen¹  Qingzhong Li¹  Wenjia Dai¹  Yan Bai²  Huawei Li³  Minxin Guan⁴ 

[1] Department of Otolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, 200031, Shanghai, China;Department of Otolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, 200031, Shanghai, China;Department of Otolaryngology, Affiliated Chongqing Children's Hospital, Chongqing Medical University, 136 Zhongshan Er Road, 400014, Chongqing, China;Department of Otolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, 200031, Shanghai, China;Institute of Biomedical Sciences, Fudan University, 20031, Shanghai, China;Department of Otolaryngology, the First Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China;

关键词: Outer Hair Cell;    Mutation Load;    Mitochondrial Haplotype;    High Penetrance;    GJB2 Gene;   

DOI  :  10.1186/1471-2350-11-129

 received in 2010-05-05, accepted in 2010-09-07,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe 1555A > G mutation is the most common cause of aminoglycoside-induced and non-syndromic deafness. However, the variable clinical phenotype and incomplete penetrance of A1555G-induced hearing loss complicate our understanding of this mutation. Environmental factors, nuclear genes, mitochondrial haplotypes/variants and a possible threshold effect have been reported to may be involved in its manifestation.MethodsHere, we performed a clinical, molecular, genetic and phylogenic analysis in a six-generation Chinese family.ResultsA clinical evaluation revealed that affected individuals without aminoglycoside exposure developed hearing loss extending gradually from 12000 Hz to 8000 Hz and then to 4000 Hz. Using pyrosequencing, we detected an identical homoplasmic 1555A > G mutation in all individuals except one. We did not find any correlation between the mutation load and the severity of hearing loss. T123N coexisted with the 1555A > G mutation in six affected subjects in our pedigree. Analysis of the complete mtDNA genome of this family revealed that this family belonged to haplotype B4C1C and exhibited high penetrance. Upon the inclusion of subjects that had been exposed to aminoglycosides, the penetrance of the hearing loss was 63.6%.; without exposure to aminoglycosides, it was 51.5%. This pedigree and another reported Chinese pedigree share the same haplotype (B4C1C) and lack functionally significant mitochondrial tRNA variants, but nevertheless they exhibit a different penetrance of hearing loss.ConclusionsOur results imply that the factors responsible for the higher penetrance and variable expression of the deafness associated with the 1555A > G mutation in this pedigree may not be mtDNA haplotype/variants, but rather nuclear genes and/or aminoglycosides.

【 授权许可】

Unknown   
© Bai et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.