Journal article
Functional characterization of novel NR5A1 variants reveals multiple complex roles in disorders of sex development
G Robevska, JA van den Bergen, T Ohnesorg, S Eggers, C Hanna, R Hersmus, EM Thompson, A Baxendale, CF Verge, AR Lafferty, NS Marzuki, A Santosa, NA Listyasari, S Riedl, G Warne, L Looijenga, S Faradz, KL Ayers, AH Sinclair
Human Mutation | WILEY-HINDAWI | Published : 2018
DOI: 10.1002/humu.23354
Open access
Abstract
Variants in the NR5A1 gene encoding SF1 have been described in a diverse spectrum of disorders of sex development (DSD). Recently, we reported the use of a targeted gene panel for DSD where we identified 15 individuals with a variant in NR5A1, nine of which are novel. Here, we examine the functional effect of these changes in relation to the patient phenotype. All novel variants tested had reduced trans-activational activity, while several had altered protein level, localization, or conformation. In addition, we found evidence of new roles for SF1 protein domains including a region within the ligand binding domain that appears to contribute to SF1 regulation of Müllerian development. There w..
View full abstractGrants
Awarded by Australian Genome Research Facility
Funding Acknowledgements
Contract Grant Sponsors: The National Health and Medical Research Council, Australia (546517); the Ian Potter Centre for Genomics and Personalised Medicine; Victorian Government's Operational Infrastructure Support Program, and the National Health and Medical Research Council Australia Independent Medical Research Institutes Infrastructure Support Scheme.