Identification of Two Novel Mutations in KDM3A Regulatory Gene in Iranian Infertile Males

Iran Biomed J. 2019 May;23(3):220-7. doi: 10.29252/.23.3.220. Epub 2018 Jul 28.


Background: KDM3A is a key epigenetic regulator expressed in the testis and is required for packaging and condensation of sperm chromatin. To this point, the association of the KDM3A gene with infertility has not been studied in human. The aim of this study was to screen any new mutation in KDM3A gene to explore more details of human male infertility.

Methods: In this work, 150 infertile men (oligozoospermia and azoospermia) and 150 normal healthy fathers were studied. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and sequencing were used to screen any mutation in exons 12, 22, and 24 of KDM3A.

Results: The infertile men showed various SSCP patterns for the exons 12 and 24, but not for exon 22. A transversion point mutation in exon 12 and a single nucleotide deletion in exon 24 were detected using sequencing analysis. The transversion mutation was located in the preceding exon of lysine-specific demethylase1 and Jumonji (Jmj)-C domain and the later one (deletion) in the cupin-like motif of KDM3A protein. Neither Y chromosome microdeletions nor partial azoospermia factor deletion was found in these patients.

Conclusion: The mutations found in infertile men with otherwise unexplained severe spermatogenic failure could be considered as the origin of their abnormalities.

Keywords: KDM3A; Male infertility; Spermatogenic failure.

MeSH terms

  • Adult
  • Azoospermia / genetics
  • Base Sequence
  • Chromosome Deletion
  • Chromosomes, Human, Y / genetics
  • Exons / genetics
  • Genetic Markers
  • Genetic Predisposition to Disease*
  • Humans
  • Infertility, Male / genetics*
  • Iran
  • Jumonji Domain-Containing Histone Demethylases / genetics*
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Polymorphism, Single-Stranded Conformational
  • Sex Chromosome Aberrations
  • Sex Chromosome Disorders of Sex Development / genetics
  • Young Adult


  • Genetic Markers
  • Jumonji Domain-Containing Histone Demethylases
  • KDM3A protein, human

Supplementary concepts

  • Male sterility due to Y-chromosome deletions