Journal article

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..

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