Identification of a novel DFNA5 mutation, IVS7-2 a > G, in a Chinese family with non-syndromic sensorineural hearing loss

Acta Otolaryngol. 2022 May;142(5):448-453. doi: 10.1080/00016489.2019.1597984. Epub 2022 May 31.


Background: To date, seven DFNA5 mutations have been reported in families with autosomal dominant non-syndromic hearing loss worldwide. All the mutations cause exon 8 skipping at the mRNA level, that led to the protein truncated and the protein could exert a gain of ototoxic function.

Objective: In this study, we found an autosomal-dominant non-syndromic hearing loss Chinese pedigree which spanned four generations and comprised 43 members. We want to identify the causative gene and mutation.

Methods: Application of microsatellite markers on DFNA 23 loci preliminary screening of 25 genes, data were analyzed by linkage analysis.

Results: We mapped the locus to the region between D7S629 and D7S516 (two-point lod-score of 5.39) with the application of 8 microsatellite markers. By direct sequencing of candidate genes in mapping region, we identified a novel missense mutation ivs7-2 A > G in DFNA5 gene, which was faithfully cosegregated with hearing loss in the family.

Conclusion and significance: The missense mutation in intron 7 of DFNA5 causes skipping of exon 8, resulting in premature termination of the open reading frame. This type of mutation has repeatedly confirmed that it provides more evidence for the previous view and provides a more solid foundation for future research.

Keywords: DFNA5; hearing loss; linkage analysis; mutation.

MeSH terms

  • China
  • Deafness / genetics
  • Hearing Loss* / genetics
  • Hearing Loss, Sensorineural* / genetics
  • Humans
  • Mutation
  • Pedigree
  • Pore Forming Cytotoxic Proteins* / genetics
  • Receptors, Estrogen / genetics


  • GSDME protein, human
  • Pore Forming Cytotoxic Proteins
  • Receptors, Estrogen

Supplementary concepts

  • Deafness, Autosomal Dominant 5
  • Nonsyndromic Deafness