Growth differentiating factor-9 mutations may be associated with premature ovarian failure.
OBJECTIVE
To determine whether perturbations of the growth differentiating factor-9 (GDF9) gene are associated with premature ovarian failure (POF).


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


METHODS
Academic institution.


METHODS
Sixty-one women with POF; 60 control women.


METHODS
Peripheral blood sampling, genomic DNA extraction, mutational screening, and DNA sequencing.


METHODS
Genetic perturbations in GDF9 that are associated with POF.


RESULTS
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.


CONCLUSIONS
GDF9 mutations may be one explanation for POF, albeit uncommon.
Kovanci
Ertug
E
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA.
Rohozinski
Jan
J
Simpson
Joe Leigh
JL
Heard
Michael J
MJ
Bishop
Colin E
CE
Carson
Sandra A
SA
D000328:Adult; D055430:Bone Morphogenetic Protein 15; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D055429:Growth Differentiation Factor 9; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D016649:Primary Ovarian Insufficiency / Q000453:epidemiology* / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D013223:Statistics as Topic; D014481:United States / Q000453:epidemiology
C525901:BMP15 protein, human; D055430:Bone Morphogenetic Protein 15; C525897:GDF9 protein, human; D055429:Growth Differentiation Factor 9; D036341:Intercellular Signaling Peptides and Proteins