Objective: To determine whether perturbations of the growth differentiating factor-9 (GDF9) gene are associated with premature ovarian failure (POF).

Design: Mutational analysis of the GDF9 gene in 61 women with POF.

Setting: Academic institution.

Patient(s): Sixty-one women with POF; 60 control women.

Intervention(s): Peripheral blood sampling, genomic DNA extraction, mutational screening, and DNA sequencing.

Main outcome measure(s): Genetic perturbations in GDF9 that are associated with POF.

Result(s): A single missense mutation, substitution of a cytosine residue with thymidine in exon 1 of GDF9, was found in a white woman in whom POF developed at age 22. This mutation occurred in a highly conserved proprotein region and resulted in replacement of a nonpolar amino acid (proline) with a polar amino acid (serine) at position 103. Neither 60 control women nor 60 other women with POF demonstrated this genetic perturbation. Exon 2 showed only previously recognized single nucleotide polymorphisms.

Conclusion(s): GDF9 mutations may be one explanation for POF, albeit uncommon.