Ten Novel Mutations in the NR5A1 Gene Cause Disordered Sex Development in 46,XY and Ovarian Insufficiency in 46,XX Individuals

Context: Steroidogenic factor-1 (SF-1/NR5A1) is a nuclear receptor that regulates adrenal and reproductive development and function. NR5A1 mutations have been detected in 46,XY individuals with disorders of sexual development (DSD) but apparently normal adrenal function and in 46,XX women with normal sexual development yet primary ovarian insufficiency (POI). Objective: A group of 100 46,XY DSD and two POI was studied for NR5A1 mutations and their impact. Design: Clinical, biochemical, histological, genetic, and functional characteristics of the patients with NR5A1 mutations are reported. Setting: Patients were referred from different centers in Spain, Switzerland, and Turkey. Histological and genetic studies were performed in Barcelona, Spain. In vitro studies were performed in Bern, Switzerland. Patients: A total of 65 Spanish and 35 Turkish patients with 46,XY DSD and two Swiss 46,XX patients with POI were investigated. Main Outcome: Ten novel heterozygote NR5A1 mutations were detected and characterize...