Four Novel Variants in POU4F3 Cause Autosomal Dominant Nonsyndromic Hearing Loss

Neural Plast. 2020 Jul 1:2020:6137083. doi: 10.1155/2020/6137083. eCollection 2020.

Abstract

Hereditary hearing loss is one of the most common sensory disabilities worldwide. Mutation of POU domain class 4 transcription factor 3 (POU4F3) is considered the pathogenic cause of autosomal dominant nonsyndromic hearing loss (ADNSHL), designated as autosomal dominant nonsyndromic deafness 15. In this study, four novel variants in POU4F3, c.696G>T (p.Glu232Asp), c.325C>T (p.His109Tyr), c.635T>C (p.Leu212Pro), and c.183delG (p.Ala62Argfs∗22), were identified in four different Chinese families with ADNSHL by targeted next-generation sequencing and Sanger sequencing. Based on the American College of Medical Genetics and Genomics guidelines, c.183delG (p.Ala62Argfs∗22) is classified as a pathogenic variant, c.696G>T (p.Glu232Asp) and c.635T>C (p.Leu212Pro) are classified as likely pathogenic variants, and c.325C>T (p.His109Tyr) is classified as a variant of uncertain significance. Based on previous reports and the results of this study, we speculated that POU4F3 pathogenic variants are significant contributors to ADNSHL in the East Asian population. Therefore, screening of POU4F3 should be a routine examination for the diagnosis of hereditary hearing loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Female
  • Hearing Loss, Sensorineural / genetics*
  • High-Throughput Nucleotide Sequencing
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Mutation, Missense*
  • Pedigree*
  • Transcription Factor Brn-3C / genetics*
  • Young Adult

Substances

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

Supplementary concepts

  • Nonsyndromic sensorineural hearing loss