GDF9 Mutation Analyses in 100 Chinese Women with Premature Ovarian Failure (POF)

We screened growth differentiation factor 9 (GDF9) coding regions for mutations in a Chinese sample of 100 women with premature ovarian failure (POF) and discovered 4 novel SNPs: c.436C>T (p.Arg146Cys), c.588A>C (silent), c.712A>G (p.Thr238Ala) and c.1283G>C (p.Ser428Thr). Non-synonymous SNPs c.436C>T and c.1283G>C were also detected in the control population. The c. 712A>G perturbation results in a missense mutation (p.Thr238Ala) and was not present in any of 96 controls. Substitution of the hydrophobic amino acid residue alanine for hydrophilic threonine may disrupt GDF9 function.

[1]  R. Baber,et al.  Premature ovarian failure: a review , 2007, Climacteric : the journal of the International Menopause Society.

[2]  D. Duffy,et al.  Novel variants in growth differentiation factor 9 in mothers of dizygotic twins. , 2006, The Journal of clinical endocrinology and metabolism.

[3]  A. Shelling,et al.  Mutational analysis of BMP15 and GDF9 as candidate genes for premature ovarian failure. , 2006, Fertility and sterility.

[4]  R. Frydman,et al.  Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure. , 2006, European journal of endocrinology.

[5]  L. Singh,et al.  Mutational screening of the coding region of growth differentiation factor 9 gene in Indian women with ovarian failure , 2005, Menopause.

[6]  S. Shimasaki,et al.  Functional and Molecular Characterization of Naturally Occurring Mutations in the Oocyte-secreted Factors Bone Morphogenetic Protein-15 and Growth and Differentiation Factor-9* , 2004, Journal of Biological Chemistry.

[7]  M. Mullen,et al.  Mutations in the Genes for Oocyte-Derived Growth Factors GDF9 and BMP15 Are Associated with Both Increased Ovulation Rate and Sterility in Cambridge and Belclare Sheep (Ovis aries)1 , 2004, Biology of reproduction.

[8]  R. Reindollar,et al.  Contemporary issues in primary amenorrhea. , 2003, Obstetrics and gynecology clinics of North America.

[9]  N. Santoro.  Mechanisms of premature ovarian failure. , 2003, Annales d'endocrinologie.

[10]  G. Montgomery,et al.  Genes controlling ovulation rate in sheep. , 2001, Reproduction.

[11]  G. Montgomery,et al.  Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner , 2000, Nature Genetics.

[12]  M. Matzuk,et al.  Molecular characterization of the follicle defects in the growth differentiation factor 9-deficient ovary. , 1999, Molecular endocrinology.

[13]  L. Dalprà,et al.  Inheritance in idiopathic premature ovarian failure: analysis of 71 cases. , 1998, Human reproduction.

[14]  D. Torgerson,et al.  Mothers and daughters menopausal ages: is there a link? , 1997, European journal of obstetrics, gynecology, and reproductive biology.

[15]  David F. Albertini,et al.  Growth differentiation factor-9 is required during early ovarian folliculogenesis , 1996, Nature.

[16]  G. Kaltsas,et al.  Characterization of idiopathic premature ovarian failure , 1996, Fertility and sterility.

[17]  D. Cramer,et al.  Family history as a predictor of early menopause. , 1995, Fertility and sterility.

[18]  J. Annegers,et al.  Incidence of Premature Ovarian Failure , 1986, Obstetrics and gynecology.

[19]  D. Lipman,et al.  Rapid similarity searches of nucleic acid and protein data banks. , 1983, Proceedings of the National Academy of Sciences of the United States of America.