Mutation analysis of the <i>SLC26A4</i> gene in three Chinese families

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Author(s)

    • Wen Cheng
    • Beijing Tongren Hospital, Capital Medical University; Beijing Institute of Otolaryngology; Key Laboratory of Otolaryngology, Head and Neck Surgery, Ministry of Education, Beijing, China.
    • Wang Shijie
    • No. 731 Hospital of China Aerospace Science and Industry Corp, Beijing, China.
    • Zhao Xuelei
    • Beijing Tongren Hospital, Capital Medical University; Beijing Institute of Otolaryngology; Key Laboratory of Otolaryngology, Head and Neck Surgery, Ministry of Education, Beijing, China.
    • Wang Xianlei
    • Beijing Tongren Hospital, Capital Medical University; Beijing Institute of Otolaryngology; Key Laboratory of Otolaryngology, Head and Neck Surgery, Ministry of Education, Beijing, China.
    • Wang Xueyao
    • Beijing Tongren Hospital, Capital Medical University; Beijing Institute of Otolaryngology; Key Laboratory of Otolaryngology, Head and Neck Surgery, Ministry of Education, Beijing, China.
    • Cheng Xiaohua
    • Beijing Tongren Hospital, Capital Medical University; Beijing Institute of Otolaryngology; Key Laboratory of Otolaryngology, Head and Neck Surgery, Ministry of Education, Beijing, China.
    • Huang Lihui
    • Beijing Tongren Hospital, Capital Medical University; Beijing Institute of Otolaryngology; Key Laboratory of Otolaryngology, Head and Neck Surgery, Ministry of Education, Beijing, China.

Abstract

<p>In order to investigate the genetic causes of hearing loss in a Chinese proband (in Family A) with enlarged vestibular aqueduct (EVA) and to investigate the genotype of two Chinese probands with <i>SLC26A4 </i>singe-allelic mutation and normal hearing (in Families B and C, respectively), the three probands and their parents were clinically and genetically evaluated. Twenty exons and flanking splice sites of the <i>SLC26A4</i> gene were screened for pathogenic mutations <i>via</i> amplification with PCR and bidirectional sequencing. As controls, a group of 400 healthy newborns from the same ethnic background underwent <i>SLC26A4 </i>gene screening using the same method. The three probands all harbored two mutations in the <i>SLC26A4</i> gene in the form of compound heterozygosity. The genotypes of mutations in Families A, B, and C are c.1211C>A/c.919-2A>G, c.1729G>A/c.919-2A>G, and c.1286C>A/c.919-2A>G, respectively. The missense mutations c.1211C>A (p.T430Q) in exon 10 and c.1729G>A (p.V577I) in exon 16 are both reported for the first time and were absent in 400 healthy newborns. c.1211C>A has Glutamine (Gln) at amino acid 430 instead of Threonine (Thr), and c.1729G>A has Isoleucine (Ile) at amino acid 577 instead of Valine (Val). c.1286C>A, a mutation previously reported in DVD and HGMD, was associated with Mondini deformity, but a proband with the c.1286C>A mutation in this study was normal. This study has demonstrated that the novel missense mutation c.1211C>A in compound heterozygosity with c.919-2A>G in the <i>SLC26A4</i> gene is likely to be the cause of deafness in Family A. A novel variant, c.1729G>A, was identified and is likely benign. The pathogenicity of the c.1286C>A mutation warrants more in-depth study. These findings will broaden the spectrum of known <i>SLC26A4</i> mutations in the Chinese population, providing more information for genetic counseling and diagnosis of hearing loss with EVA.</p>

Journal

  • BioScience Trends

    BioScience Trends 13(5), 441-447, 2019

    International Research and Cooperation Association for Bio & Socio-Sciences Advancement

Codes

  • NII Article ID (NAID)
    130007744275
  • Text Lang
    ENG
  • ISSN
    1881-7815
  • Data Source
    J-STAGE 
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