Limited contribution of NR5A1 (SF-1) mutations in women with primary ovarian insufficiency (POI)

• Published in: Fertility and sterility Vol. 97; no. 1; pp. 141 - 146.e2
• Main Authors: Janse, Femi, de With, Larissa M., Duran, Karen J., Kloosterman, Wigard P., Goverde, Angelique J., Lambalk, Cornelius B., Laven, Joop S.E., Fauser, Bart C.J.M., Giltay, Jacques C.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 2012; Elsevier
• Subjects: Adolescent; Adult; amenorrhea; animal ovaries; Biological and medical sciences; cohort studies; Cross-Sectional Studies; Female; genes; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; Genetic Testing; Gynecology. Andrology. Obstetrics; Humans; Internal Medicine; Medical sciences; Middle Aged; mutation; NR5A1; Obstetrics and Gynecology; pathogenicity; patients; Phenotype; POI; Point Mutation - genetics; prediction; Primary ovarian insufficiency; Primary Ovarian Insufficiency - epidemiology; Primary Ovarian Insufficiency - genetics; RNA Splice Sites - genetics; sexual development; SF-1; steroidogenic factor 1; Steroidogenic Factor 1 - genetics; women; Young Adult; NR5A1; SF-1; POI; steroidogenic factor 1; Primary ovarian insufficiency; Endocrinopathy; Human; Gynecology; Obstetrics; Female genital diseases; Ovarian diseases; Steroidogenic factor-1; Ovarian failure; Primary; Female; Mutation; Woman
• ISSN: 0015-0282; 1556-5653; 1556-5653
• DOI: 10.1016/j.fertnstert.2011.10.032

To evaluate the significance of NR5A1 mutations in a large, well-phenotyped cohort of women with primary ovarian insufficiency (POI). Mutations in the NR5A1 gene (SF-1) were previously described in disorders of sexual development and adrenal insufficiency. Recently, a high frequency of NR5A1 gene mutations was reported in a small group of women with POI. Cross-sectional cohort study. University hospital. Well-phenotyped women (n = 386) with secondary amenorrhea and diagnosed with POI, including women with familial POI (n = 77). None. The entire coding region and splice sites of the NR5A1 gene were PCR-amplified and sequenced. The pathogenicity of identified mutations was predicted in silico by assessing Align-GVGD class and Grantham score. Sequencing was successful in 356 patients with POI. In total, 9 mutations were identified in 10 patients. Five of these mutations concerned novel nonconservative mutations occurring in 5 patients. Prediction of effect on protein function showed low to intermediate pathogenicity for all nonconservative mutations. The overall NR5A1 gene mutation rate was 1.4%. The current study demonstrates that mutations in the NR5A1 gene are rare in women with POI. Primary ovarian insufficiency remains unexplained in the great majority of patients; therefore, continued efforts are needed to elucidate its underlying genetic factors.