- 作者：Pascal Philibert ; Pharm.D. ; Ph.D.a ; Franç ; oise Paris ; M.D. ; Ph.D.a ; b ; Besma Lakhal ; Ph.D.c ; Franç ; oise Audran ; Pharm.D.a ; Laura Gaspari ; M.D.a ; b ; Ali Saâ ; d ; M.D. ; Ph.D.c ; Sophie Christin-Maî ; tre ; M.D. ; Ph.D.d ; Philippe Bouchard ; M.D. ; Ph.D.d ; Charles Sultan ; M.D. ; Ph.D.b ; c ; c-sultan@chu-montpellier.fr
- 关键词：Primary ovarian insufficiency ; NR5A1/SF-1 mutant ; sex differentiation ; ovarian function
- 刊名：Fertility and Sterility
- 出版年：2013
- 出版时间：February, 2013
- 年：2013
- 卷：99
- 期：2
- 页码：484-489
- 全文大小：565 K
Objective
To determine whether NR5A1 (SF-1) variants are a cause of primary ovarian insufficiency (POI) in 26 young women with similar genetic background.Design
Genetic and functional mutation study.
Setting
University hospitals.
Patient(s)
Genetic analysis of the NR5A1 gene in 26 XX girls with POI.
Intervention(s)
None.
Main Outcome Measure(s)
NR5A1 molecular and functional analysis.
Result(s)
Genetic analysis revealed a new c.763C>T (p.Arg255Cys) mutation and a recurrent c.437G>C (p.Gly146Ala) variant. Functional analysis of the p.Arg255Cys mutant showed a marked decrease in transactivation on the Cyp11a1 and Amh promoters. The p.Gly146Ala variant was identified significantly more often in the patients (46.1 % ) than in ancestry-matched control subjects (10 % ).
Conclusion(s)
We identified one new NR5A1 mutation in a patient of our POI cohort (prevalence 3.8 % ). Moreover, although our study is limited in the number of cases, we report the high frequency of the p.Gly146Ala variant in this cohort compared with the ancestry-matched control subjects. This work highlights the important role of SF-1 in ovarian function.