Identification of a novel splicing mutation within SLC17A8 in a Korean family with hearing loss by whole-exome sequencing

Gene. 2017 Sep 5:627:233-238. doi: 10.1016/j.gene.2017.06.040. Epub 2017 Jun 21.

Abstract

Hereditary hearing loss (HHL) is a common genetically heterogeneous disorder, which follows Mendelian inheritance in humans. Because of this heterogeneity, the identification of the causative gene of HHL by linkage analysis or Sanger sequencing have shown economic and temporal limitations. With recent advances in next-generation sequencing (NGS) techniques, rapid identification of a causative gene via massively parallel sequencing is now possible. We recruited a Korean family with three generations exhibiting autosomal dominant inheritance of hearing loss (HL), and the clinical information about this family revealed that there are no other symptoms accompanied with HL. To identify a causative mutation of HL in this family, we performed whole-exome sequencing of 4 family members, 3 affected and an unaffected. As the result, A novel splicing mutation, c.763+1G>T, in the solute carrier family 17, member 8 (SLC17A8) gene was identified in the patients, and the genotypes of the mutation were co-segregated with the phenotype of HL. Additionally, this mutation was not detected in 100 Koreans with normal hearing. Via NGS, we detected a novel splicing mutation that might influence the hearing ability within the patients with autosomal dominant non-syndromic HL. Our data suggests that this technique is a powerful tool to discover causative genetic factors of HL and facilitate diagnoses of the primary cause of HHL.

Keywords: Gene; Hearing loss; Next-generation sequencing; SLC17A8; Splicing mutation.

MeSH terms

  • Adult
  • Aged
  • Exome
  • Female
  • Hearing Loss / genetics*
  • Humans
  • Male
  • Mutation*
  • Pedigree
  • RNA Splicing*
  • Republic of Korea
  • Vesicular Glutamate Transport Proteins / genetics*

Substances

  • SLC17A8 protein, human
  • Vesicular Glutamate Transport Proteins