Novel mutation in the homeobox domain of transcription factor POU3F4 associated with profound sensorineural hearing loss

Otol Neurotol. 2011 Jun;32(4):690-4. doi: 10.1097/MAO.0b013e318210b749.


Background: Hearing loss affects 1 to 3 in 1,000 newborns, with 50% of these cases because of genetic causes. The majority of these are nonsyndromic (70%), and 2% are X linked. So far, 6 different X-linked loci have been mapped, but the causative gene POU3F4 has been identified only for the Locus DFN3. Clinical features of DFN3 often include a mixed, progressive hearing loss, temporal bone anomalies, and stapes fixation. POU3F4 belongs to a subfamily of transcription factors, which are characterized by 2 conserved deoxyribonucleic acid-binding domains, a POU and a HOX domain, both helix-turn-helix structural deoxyribonucleic acid-binding motifs.Several reports have described mutations of POU3F4 in patients with hearing loss and temporal bone abnormalities. In this study, we describe the clinical features and genetic analysis of a male child from a German family with congenital deafness and a novel POU3F4 mutation.

Method: Mutational analysis of the affected individual and first-degree relatives was performed using direct sequencing of the coding exon and intron transitions of POU3F4.

Result: The patient (II-1) had profound hearing loss, a severely dysplastic cochlea, and cerebrospinal fluid gusher during cochlear implantation. Sequence analysis of all family members demonstrated a novel missense mutation at nucleotide position 973, thymine to adenine (c.973 T>A), p.W325R in the patient (II-1), the mother (I-2), and sisters (II-2, II-3) heterozygous. The father (I-1) is not a carrier of the mutation. Conservation of the affected amino acid residue was seen across a number of different species.

Conclusion: We identified a novel mutation in the third helix of the HOX domain of the POU3F4 transcription factor associated with congenital hearing loss.

Publication types

  • Case Reports

MeSH terms

  • Child
  • DNA Mutational Analysis
  • Hearing Loss, Bilateral / genetics*
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Male
  • Mutation
  • POU Domain Factors / genetics*


  • POU Domain Factors
  • POU3F4 protein, human