NR5A1 is a novel disease gene for 46,XX testicular and ovotesticular disorders of sex development.

ABSTRACT:

Purpose

We aimed to identify the genetic cause in a cohort of 11 unrelated cases and two sisters with 46,XX SRY-negative (ovo)testicular disorders of sex development (DSD).

Methods

Whole-exome sequencing (n = 9), targeted resequencing (n = 4), and haplotyping were performed. Immunohistochemistry of sex-specific markers was performed on patients' gonads. The consequences of mutation were investigated using luciferase assays, localization studies, and RNA-seq.

Results

We identified a novel heterozygous NR5A1 mutation, c.274C>T p.(Arg92Trp), in three unrelated patients. The Arg92 residue is highly conserved and located in the Ftz-F1 region, probably involved in DNA-binding specificity and stability. There were no consistent changes in transcriptional activation or subcel

SUBMITTER: Baetens D 

PROVIDER: S-EPMC5392598 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature