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

作者：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

来源：Fertility and Sterility, 2012, 97(1): 141-U205.

DOI：10.1016/j.fertnstert.2011.10.032

• Primary ovarian insufficiency
• POI
• steroidogenic factor 1
• SF-1
• NR5A1

Objective: 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. %26lt;br%26gt;Design: Cross-sectional cohort study. %26lt;br%26gt;Setting: University hospital. %26lt;br%26gt;Patient(s): Well-phenotyped women (n = 386) with secondary amenorrhea and diagnosed with POI, including women with familial POI (n 77). %26lt;br%26gt;Intervention(s): None. %26lt;br%26gt;Main Outcome Measure(s): 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. %26lt;br%26gt;Result(s): 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%. %26lt;br%26gt;Conclusion(s): 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. (Fertil Steril (R) 2012;97:141-6.

• 出版日期2012-1