NR5A1 gene variants repress the ovarian-specific WNT signaling pathway in 46,XX disorders of sex development patients
Ingrid M Knarston, Gorjana Robevska, Jocelyn A van den Bergen, Stefanie Eggers, Brittany Croft, Jason Yates, Remko Hersmus, Leendert HJ Looijenga, Fergus J Cameron, Klaus Monhike, Katie L Ayers, Andrew H Sinclair
HUMAN MUTATION | WILEY | Published : 2019
Several recent reports have described a missense variant in the gene NR5A1 (c.274C>T; p.Arg92Trp) in a significant number of 46,XX ovotesticular or testicular disorders of sex development (DSDs) cases. The affected residue falls within the DNA-binding domain of the NR5A1 protein, however the exact mechanism by which it causes testicular development in 46,XX individuals remains unclear. We have screened a cohort of 26 patients with 46,XX (ovo)testicular DSD and identified three unrelated individuals with this NR5A1 variant (p.Arg92Trp), as well as one patient with a novel NR5A1 variant (c.779C>T; p.Ala260Val). We examined the functional effect of these changes, finding that while protein leve..View full abstract
Awarded by National Health and Medical Research Council, Australia
This research was supported by The National Health and Medical Research Council, Australia (Program grant number 546517).