A novel splice site mutation in DFNA5 causes late-onset progressive non-syndromic hearing loss in a Chinese family

Int J Pediatr Otorhinolaryngol. 2014 Aug;78(8):1265-8. doi: 10.1016/j.ijporl.2014.05.007. Epub 2014 May 21.

Abstract

Objectives: Mutations in DFNA5 may lead to autosomal dominant non-syndromic sensorineural hearing loss (NSHL). To date, only four DFNA5 mutations have been reported, all resulting in skipping of exon 8 at the mRNA level. In this study, we aim to characterize the clinical features and the genetic cause of a Chinese DFNA5 family.

Methods: Targeted next-generation sequencing of 79 known deafness genes was performed in the proband. Co-segregation between the disease phenotype and the potentially pathogenic variant was confirmed in all family members by Sanger sequencing.

Results: A novel heterozygous c.991-2A>G mutation in DFNA5 was identified in this family segregating with the autosomal dominant, late-onset NSHL. This mutation was located in the conventional splice site in intron 7 and was likely to result in skipping of exon 8. The severity of hearing impairment varied intrafamilially.

Conclusion: We identified a novel c.991-2A>G mutation in DFNA5 which again may lead to exon 8 skipping at the mRNA level. Our findings supported that the DFNA5-associated NSHL results from a specific gain-of-function mechanism.

Keywords: Autosomal dominant hearing loss; DFNA5; Spice site mutation; Target next-generation sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Asian People / genetics
  • Child
  • China
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Inteins / genetics
  • Mutation*
  • Pedigree
  • RNA Splicing
  • Receptors, Estrogen / genetics*
  • Severity of Illness Index

Substances

  • GSDME protein, human
  • Receptors, Estrogen