A missense mutation in NR5A1 causing female to male sex reversal: A case report

Masomeh Askari (1) , Mandana Rastari (1, 2) , Mehrshad Seresht‐ahmadi (1, 2) , Ken Mcelreavey (3) , Anu Bashamboo (3) , Maryam Razzaghy‐azar (4) , Mehdi Totonchi (5, 1)

1 ACECR - Academic Center for Education, Culture and Research
2 USC - University of Science and Culture
3 Génétique du Développement humain - Human developmental genetics
4 TUMS - Tehran University of Medical Sciences
5 Royan Institute for Reproductive Biomedicine [Tehran, Iran]

Testicular disorder of sex development (TDSD) is a rare condition, characterised by a female karyotype, male phenotype, small testes and cryptorchidism. Only a few studies have investigated the genetic causes of male sex reversal. This is the clinical report of an Iranian 46,XX patient presented with TDSD and associated with hypospadias. Whole-exome sequencing (WES) of the patient ascertained the heterozygous missense variant (c.274C>T) in the NR5A1 gene, resulting in a substitution of arginine with tryptophan. The arginine 92 residue was located in a highly conserved region of steroidogenic factor 1 (SF1), which is crucial for its interaction with DNA. Our finding is in line with previous reports, which highlighted the role of p.(Arg92Trp) variant in TDSD individuals. As far as we are aware, this is the first report of TDSD with p.(Arg92Trp) variant in the Iranian population.

Mots clés: NR5A1; sex reversal; testicular DSD

Domaines: Sciences du Vivant [q-bio]

Masomeh Askari, Mandana Rastari, Mehrshad Seresht‐ahmadi, Ken Mcelreavey, Anu Bashamboo, et al.. A missense mutation in NR5A1 causing female to male sex reversal: A case report. Andrologia, 2020, 52 (6), pp.e13585. ⟨10.1111/and.13585⟩. ⟨pasteur-03521830⟩