When transcripts matter: delineating between non-syndromic hearing loss DFNB32 and hearing impairment infertile male syndrome (HIIMS)

J Hum Genet. 2020 Jul;65(7):609-617. doi: 10.1038/s10038-020-0740-z. Epub 2020 Mar 30.


Mutations in the CDC14A (Cell Division-Cycle 14A) gene, which encodes a conserved dual-specificity protein tyrosine phosphatase, have been identified as a cause of autosomal recessive non-syndromic hearing loss (DFNB32) and hearing impairment infertility male syndrome (HIIMS). We used next-generation sequencing to screen six deaf probands from six families segregating sensorineural moderate-to-profound hearing loss. Data analysis and variant prioritization were completed using a custom bioinformatics pipeline. We identified three homozygous loss of function variants (p.Arg345Ter, p.Arg376Ter, and p.Ala451Thrfs*43) in the CDC14A gene, segregating with deafness in each family. Of the six families, four segregated the p.Arg376Ter mutation, one family segregated the p.Arg345Ter mutation and one family segregated a novel frameshift (p.Ala451Thrfs*43) mutation. In-depth phenotyping of affected individuals ruled out secondary syndromic findings. This study implicates the p.Arg376Ter mutation might be as a founder mutation in the Iranian population. It also provides the first semen analysis for deaf males carrying mutations in exon 11 of CDC14A and reveals a genotype-phenotype correlation that delineates between DFNB32 and HIIMS. The clinical results from affected males suggest the NM_033313.2 transcript alone is sufficient for proper male fertility, but not for proper auditory function. We conclude that DFNB32 is a distinct phenotypic entity in males.

MeSH terms

  • Adolescent
  • Adult
  • Diagnosis, Differential
  • Exons / genetics
  • Female
  • Frameshift Mutation / genetics
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Hearing Loss / complications
  • Hearing Loss / diagnosis
  • Hearing Loss / genetics*
  • Hearing Loss / pathology
  • Hearing Loss, Sensorineural / complications
  • Hearing Loss, Sensorineural / diagnosis
  • Hearing Loss, Sensorineural / genetics*
  • Hearing Loss, Sensorineural / pathology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infertility, Male / complications
  • Infertility, Male / diagnosis
  • Infertility, Male / genetics*
  • Infertility, Male / pathology
  • Iran
  • Male
  • Pedigree
  • Protein Tyrosine Phosphatases / genetics*
  • Young Adult


  • CDC14A protein, human
  • Protein Tyrosine Phosphatases

Supplementary concepts

  • Deafness, Autosomal Recessive 32