Identification of SLC26A4 c.919-2A>G compound heterozygosity in hearing-impaired patients to improve genetic counseling

Journal of Translational Medicine

Research

Qing-wen Zhu¹  Dong-yi Han¹  De-liang Huang¹  Sha-sha Huang²  Yong-yi Yuan²  Pu Dai²  Qi Li³ 

[1] Department of Otolaryngology - Head and Neck Surgery, PLA General Hospital, 100853, Beijing, China;Department of Otolaryngology - Head and Neck Surgery, PLA General Hospital, 100853, Beijing, China;Department of Otolaryngology - Head and Neck Surgery, Hainan Branch of PLA General Hospital, 572000, Sanya, China;Division of Pediatric Otolaryngology, Nanjing Children’s Hospital, Nanjing Medical University, 210008, Nanjing, Jiangsu, China;

关键词: Hearing Loss;    SLC26A4 Gene;    Splice Site Mutation;    Deaf Individual;    GJB2 Gene;   

DOI  :  10.1186/1479-5876-10-225

 received in 2012-08-07, accepted in 2012-11-12,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundMutations in the SLC26A4 gene, which encodes the anion transporter, pendrin, are a major cause of autosomal recessive non-syndromic hearing loss (NSHL) in some Asian populations. SLC26A4 c.919-2A>G (IVS7-2A>G) is the most common mutation in East Asian deaf populations. To provide a basis for improving the clinical diagnosis of deaf patients, we evaluated 80 patients with the SLC26A4 c.919-2A>G monoallelic mutation from 1065 hearing-impaired subjects and reported the occurrence of a second mutant allele in these patients.MethodsThe occurrence of a second mutant allele in these 80 patients with a single c.919-2A>G mutation was investigated. Mutation screening was performed by bidirectional sequencing in SLC26A4 exons 2 to 6 and 9 to 21.ResultsWe found that 47/80 patients carried another SLC26A4 c.919-2A>G compound mutation. The five most common mutations were: p.H723R, p.T410M, 15+5G>A (c.1705+5G>A), p.L676Q and p.N392Y. We found a Chinese-specific SLC26A4 mutation spectrum and an associated SLC26A4 contribution to deafness.ConclusionOur study illustrates that mutation analysis of other SLC26A4 exons should be undertaken in deaf patients with a single heterozygous SLC26A4 mutation. Moreover, a model of compound heterozygosity may partially explain the disease phenotype.

【 授权许可】

Unknown   
© Li et al.; licensee BioMed Central Ltd. 2012. 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.