Evaluation of the contribution of the EYA4 and GRHL2 genes in Korean patients with autosomal dominant non-syndromic hearing loss

PLoS One. 2015 Mar 17;10(3):e0119443. doi: 10.1371/journal.pone.0119443. eCollection 2015.

Abstract

EYA4 and GRHL2 encode transcription factors that play an important role in regulating many developmental stages. Since EYA4 and GRHL2 were identified as the transcription factors for the DFNA10 and DFNA28, 8 EYA4 mutations and 2 GRHL2 mutations have been reported worldwide. However, these genes have been reported in few studies of the Korean population. In this study, we performed a genetic analysis of EYA4 and GRHL2 in 87 unrelated Korean patients with autosomal dominant non-syndromic hearing loss (NSHL). A total of 4 genetic variants in the EYA4 gene were identified, including the 2 nonsense mutations p.S288X and p.Q393X. The novel mutation p.Q393X (c.1177C>T) resulted in a change in the codon at amino acid position 393 from a glutamine to a stop codon. The p.Q393X allele was predicted to encode a truncated protein lacking the entire C-terminal Eya homolog region (Eya HR), which is essential for the interaction with the transcription factor SIX3. The p.S288X (c.863C>A) mutation was found in a Korean family from a previous study. We analyzed p.S288X-linked microsatellite markers and determined that p.S288X might be a founder mutation and a hotspot mutation in Koreans. In GRHL2, a total of 4 genetic variants were identified, but none were associated with hearing loss in Korean patients. This suggests that GRHL2 may not be a main causal gene for autosomal dominant NSHL in Korean patients. In conclusion, our data provide fundamental information to predict the genotypes of Korean patients diagnosed with autosomal dominant NSHL.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amino Acid Sequence
  • Asian People / genetics
  • Case-Control Studies
  • Child
  • Child, Preschool
  • DNA-Binding Proteins / genetics*
  • Female
  • Genes, Dominant*
  • Genotype
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation / genetics*
  • Pedigree
  • Polymerase Chain Reaction
  • Tandem Repeat Sequences / genetics*
  • Trans-Activators / genetics*
  • Transcription Factors / genetics*
  • Young Adult

Substances

  • DNA-Binding Proteins
  • EYA4 protein, human
  • GRHL2 protein, human
  • Trans-Activators
  • Transcription Factors

Supplementary concepts

  • Deafness, Autosomal Dominant 10
  • Deafness, Autosomal Dominant 28

Grants and funding

This research was supported by a grant from the Korean Health Technology Research & Development Project, Ministry of Health & Welfare, Republic of Korea (HI12C1004). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.