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

Background: KDM3A is a key epigenetic regulator that is expressed in the testis and is required for packaging and condensation of sperm chromatin. To this point, the association of the KDM3A gene and 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 for 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.