A Missense Mutation in POU4F3 Causes Midfrequency Hearing Loss in a Chinese ADNSHL Family

Biomed Res Int. 2018 Apr 4;2018:5370802. doi: 10.1155/2018/5370802. eCollection 2018.


Hereditary nonsyndromic hearing loss is extremely heterogeneous. Mutations in the POU class 4 transcription factor 3 (POU4F3) are known to cause autosomal dominant nonsyndromic hearing loss linked to the loci of DFNA15. In this study, we describe a pathogenic missense mutation in POU4F3 in a four-generation Chinese family (6126) with midfrequency, progressive, and postlingual autosomal dominant nonsyndromic hearing loss (ADNSHL). By combining targeted capture of 129 known deafness genes, next-generation sequencing, and bioinformatic analysis, we identified POU4F3 c.602T>C (p.Leu201Pro) as the disease-causing variant. This variant cosegregated with hearing loss in other family members but was not detected in 580 normal controls or the ExAC database and could be classified as a "pathogenic variant" according to the American College of Medical Genetics and Genomics guidelines. We conclude that POU4F3 c.602T>C (p.Leu201Pro) is related to midfrequency hearing loss in this family. Routine examination of POU4F3 is necessary for the genetic diagnosis of midfrequency hearing loss.

MeSH terms

  • Adult
  • Aged
  • Amino Acid Sequence
  • Asian People / genetics*
  • Base Sequence
  • Child, Preschool
  • DNA Mutational Analysis
  • Family
  • Female
  • Hearing Loss, Sensorineural / genetics*
  • Homeodomain Proteins / chemistry
  • Homeodomain Proteins / genetics*
  • Humans
  • Middle Aged
  • Mutation, Missense / genetics*
  • Pedigree
  • Transcription Factor Brn-3C / chemistry
  • Transcription Factor Brn-3C / genetics*


  • Homeodomain Proteins
  • POU4F3 protein, human
  • Transcription Factor Brn-3C

Supplementary concepts

  • Nonsyndromic sensorineural hearing loss