- 作者：Femi Janse ; M.D.a ; f.janse@umcutrecht.nl ; Larissa M. de With ; M.D.b ; Karen J. Duran ; Ph.D.b ; Wigard P. Kloosterman ; Ph.D.b ; Angelique J. Goverde ; M.D. ; Ph.D.a ; Cornelius B. Lambalk ; M.D. ; Ph.D.c ; Joop S.E. Laven ; M.D. ; Ph.D.d ; Bart C.J.M. Fauser ; M.D. ; Ph.D.a ; Jacques C. Giltay ; M.D. ; Ph.D.b ; the Dutch Primary Ovarian Insufficiency Consortium
- 关键词：Primary ovarian insufficiency ; POI ; steroidogenic factor 1 ; SF-1 ; NR5A1
- 刊名：Fertility and Sterility
- 出版年：2012
- 出版时间：January, 2012
- 年：2012
- 卷：97
- 期：1
- 页码：141-146.e2
- 全文大小：148 K
class=""h4"">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.class=""h4"">Design
Cross-sectional cohort study.
class=""h4"">Setting
University hospital.
class=""h4"">Patient(s)
Well-phenotyped women (n = 386) with secondary amenorrhea and diagnosed with POI, including women with familial POI (n = 77).
class=""h4"">Intervention(s)
None.
class=""h4"">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.
class=""h4"">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 % .
class=""h4"">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.