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Fertil Steril. 2012 Jan;97(1):141-6.e2. doi: 10.1016/j.fertnstert.2011.10.032. Epub 2011 Nov 17.

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

Author information

  • 1Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Utrecht, The Netherlands. f.janse@umcutrecht.nl

Abstract

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.

DESIGN:

Cross-sectional cohort study.

SETTING:

University hospital.

PATIENT(S):

Well-phenotyped women (n = 386) with secondary amenorrhea and diagnosed with POI, including women with familial POI (n = 77).

INTERVENTION(S):

None.

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.

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%.

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.

Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

[PubMed - indexed for MEDLINE]
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