Identification of SLC26A4 c.919-2A>G compound heterozygosity in hearing-impaired patients to improve genetic counseling
1 Division of Pediatric Otolaryngology, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210008, China
2 Department of Otolaryngology - Head and Neck Surgery, PLA General Hospital, Beijing, 100853, China
3 Department of Otolaryngology - Head and Neck Surgery, Hainan Branch of PLA General Hospital, Sanya, 572000, China
Journal of Translational Medicine 2012, 10:225 doi:10.1186/1479-5876-10-225Published: 14 November 2012
Mutations 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.
The 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.
We 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.
Our 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.