Research article

Screening for known mutations in EIF2B genes in a large panel of patients with premature ovarian failure

Anne Fogli¹ , Fernande Gauthier-Barichard¹ , Raphael Schiffmann² , Vien H Vanderhoof³ , Vladimir K Bakalov³ , Lawrence M Nelson³ and Odile Boespflug-Tanguy¹

¹  INSERM UMR 384, Faculté de Médecine, 28 place Henri Dunant BP 38, 63001 Clermont-Ferrand cedex, France

²  Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA

³  National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA

author email corresponding author email

BMC Women's Health 2004, 4:8doi:10.1186/1472-6874-4-8

Published:	26 October 2004

Abstract

Background

Premature Ovarian Failure (POF), defined as the development of hypergonadotropic amenorrhea before the age of 40 years, occurs in about 1% of all women. Other than karyotype abnormalities, very few genes are known to be associated with this ovarian dysfunction. Recently, in seven patients who presented with POF and white matter abnormalities on MRI (ovarioleukodystrophy) eight mutationswere found in EIF2B2, 4 and 5.

Methods

To further test the involvement of known mutations of EIF2B genes in POF, we screened 93 patients with POF who did not have identified leukodystrophy or neurological symptoms. We evaluated these eight mutations and two additional mutations that had been found in patients with milder forms of eIF2B-related disorders. We used restriction enzymes and direct sequencing.

Results

None of the known mutations in EIF2B genes, either homozygous or heterozygous, were identified in our 93 patients with pure 46,XX POF. The upper 95 % confidence limit of the proportion 0/93 is 3.2%.

Conclusions

We conclude that eIF2B mutations, already described in cases of POF associated with white matter abnormalities, are an uncommon cause of pure spontaneous premature ovarian failure.