title: Mutational screening of the NR5A1 in azoospermia.
abstract: Nuclear receptor subfamily 5 group A member 1 (NR5A1) encodes a nuclear receptor that regulates transcription of multiple genes involved in adrenal and gonadal development, steroidogenesis and the reproductive axis. Human mutations in NR5A1were 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 NR5A1 may also contribute to the male infertility aetiology. We have analysed the coding sequence of NR5A1 in a cohort of 90 well-characterised idiopathic Iranian azoospermic infertile men versus 112 fertile men. Heterozygous NR5A1 mutations were found in 2 of 90 (2.2%) of cases. These two patients harboured missense mutations within the hinge region (p.P97T) and ligand-binding domain (p.E237K) of the NR5A1 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 NR5A1 gene are not common in azoospermia, and male infertility and inclusion of NR5A1 mutation screening in the diagnostic workup of male infertility may seem unnecessary.
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: D
authors.initials: D
authors.lastname: Zare-Abdollahi
authors.forename: S
authors.initials: S
authors.lastname: Safari
authors.forename: R
authors.initials: R
authors.lastname: Mirfakhraie
authors.forename: A
authors.initials: A
authors.lastname: Movafagh
authors.forename: M
authors.initials: M
authors.lastname: Bastami
authors.forename: P
authors.initials: P
authors.lastname: Azimzadeh
authors.forename: N
authors.initials: N
authors.lastname: Salsabili
authors.forename: W
authors.initials: W
authors.lastname: Ebrahimizadeh
authors.forename: S
authors.initials: S
authors.lastname: Salami
authors.forename: M D
authors.initials: MD
authors.lastname: Omrani
mesh_terms: D000328:Adult; D053713:Azoospermia / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D054339:Steroidogenic Factor 1 / Q000235:genetics*; D055815:Young Adult
chemical_list: C515057:NR5A1 protein, human; D054339:Steroidogenic Factor 1
keywords: Azoospermia; NR5A1; male infertility; nuclear receptor; nuclear receptor subfamily 5 group A member 1