De novo mutation in X-linked hearing loss-associated POU3F4 in a sporadic case of congenital hearing loss

Ann Otol Rhinol Laryngol. 2015 May;124 Suppl 1(1 0):169S-76S. doi: 10.1177/0003489415575042. Epub 2015 Mar 19.


Objectives: In this report, we present a male patient with no family history of hearing loss, in whom we identified a novel de novo mutation in the POU3F4 gene.

Methods: One hundred ninety-four (194) Japanese subjects from unrelated and nonconsanguineous families were enrolled in this study. We used targeted genomic enrichment and massively parallel sequencing of all known nonsyndromic hearing loss genes for identifying the genetic causes of hearing loss.

Results: A novel de novo frameshift mutation of POU3F4 to c.727_728insA (p.N244KfsX26) was identified. The patient was a 7-year-old male with congenital progressive hearing loss and inner ear deformity. Although the patient had received a cochlear implant, auditory skills were still limited. The patient also exhibited developmental delays similar to those previously associated with POU3F4 mutation.

Conclusion: This is the first report of a mutation in POU3F4 causing hearing loss in a Japanese patient without a family history of hearing loss. This study underscores the importance of comprehensive genetic testing of patients with hearing loss for providing accurate prognostic information and guiding the optimal management of patient rehabilitation.

Keywords: POU3F4; cochlear implant; genetics; hearing loss; massively parallel sequencing.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Asian Continental Ancestry Group / genetics
  • Child
  • DNA Mutational Analysis
  • Deafness / genetics
  • Developmental Disabilities / genetics
  • Evoked Potentials, Auditory, Brain Stem
  • Female
  • Frameshift Mutation*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • POU Domain Factors / genetics*


  • POU Domain Factors
  • POU3F4 protein, human

Supplementary concepts

  • Nonsyndromic Deafness