title: Identification of SLC26A4 c.919-2A>G compound heterozygosity in hearing-impaired patients to improve genetic counseling.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pediatric Otolaryngology, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing, Jiangsu 210008, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Qing-wen
authors.initials: QW
authors.lastname: Zhu
authors.forename: Yong-yi
authors.initials: YY
authors.lastname: Yuan
authors.forename: Sha-sha
authors.initials: SS
authors.lastname: Huang
authors.forename: Dong-yi
authors.initials: DY
authors.lastname: Han
authors.forename: De-liang
authors.initials: DL
authors.lastname: Huang
authors.forename: Pu
authors.initials: P
authors.lastname: Dai
mesh_terms: D017931:DNA Primers; D005817:Genetic Counseling; D034381:Hearing Loss / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D011787:Quality of Health Care; D000076988:Sulfate Transporters
chemical_list: D017931:DNA Primers; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters