Mutational screening of the NR5A1 in azoospermia

Summary Nuclear receptor subfamily 5 group A member 1 ( NR 5 A 1 ) encodes a nuclear receptor that regulates transcription of multiple genes involved in adrenal and gonadal development, steroidogenesis and the reproductive axis. Human mutations in NR 5 A 1 were initially found in two 46, XY female patients suffering from severe gonadal dysgenesis and primary adrenal failure. However, more recent case reports have suggested that heterozygous mutations in NR 5 A 1 may also contribute to the male infertility aetiology. We have analysed the coding sequence of NR 5 A 1 in a cohort of 90 well‐characterised idiopathic Iranian azoospermic infertile men versus 112 fertile men. Heterozygous NR 5 A 1 mutations were found in 2 of 90 (2.2%) of cases. These two patients harboured missense mutations within the hinge region (p. P 97 T ) and ligand‐binding domain (p. E 237 K ) of the NR 5 A 1 protein. In silico analysis of the mutations showed that founded mutations could be detrimental. In conclusion, findings of the current and previous studies suggest that mutations in the NR 5 A 1 gene are not common in azoospermia, and male infertility and inclusion of NR 5 A 1 mutation screening in the diagnostic workup of male infertility may seem unnecessary.