title: Mutational screening of the coding region of growth differentiation factor 9 gene in Indian women with ovarian failure.
abstract: OBJECTIVE
  To establish the risk associated with mutations in the coding region of GDF9 gene in Indian women with ovarian failure.
  
  
  METHODS
  This case-control study was designed for mutational analysis of the GDF9 coding region in a cohort of women with premature ovarian failure (n = 127), primary amenorrhea (n = 58), and secondary amenorrhea (n = 10) compared with controls (n = 220).
  
  
  RESULTS
  This case-control study revealed eight mutations in the GDF9 gene, including five novel mutations: c.1-8C>T, c.199A>C (p.Lys67Glu), c. 205C>T, c.646G>A (p.Val216Mat), and c.1353C>T, and three documented mutations: c.398-39C>G, c.447C>T, and c.546G>A. Missense mutation c.199A>C was present in 4 of 127 premature ovarian failure (POF) cases and 1 of 10 secondary amenorrhea cases. The c.646G>A mutation was present in two POF cases. Both missense mutations were absent in controls. Genotype distribution of c.447C>T was significantly different in POF cases than controls (chi(2) = 5.93, P = 0.05). We chose two frequent single-nucleotide polymorphisms (c.398-39C>G, c.447C>T) for haplotyping and found that the C-T haplotype was significantly higher in patients (P = 0.03), whereas the C-C haplotype was representative of the control group.
  
  
  CONCLUSIONS
  We report two rare missense mutations, c.199A>C and c.646G>A, which are associated with ovarian failure. The presence of the c.447>T mutation might indicate a higher risk for POF. Haplotype C-T was significantly associated with ovarian failure, whereas the C-C haplotype was representative of the control group.
authors.affiliation: Centre for Cellular and Molecular Biology, Hyderabad, India.
authors.forename: Hridesh
authors.initials: H
authors.lastname: Dixit
authors.forename: Lakshmi K
authors.initials: LK
authors.lastname: Rao
authors.forename: Venkata
authors.initials: V
authors.lastname: Padmalatha
authors.forename: Murthy
authors.initials: M
authors.lastname: Kanakavalli
authors.forename: Mamatha
authors.initials: M
authors.lastname: Deenadayal
authors.forename: Nalini
authors.initials: N
authors.lastname: Gupta
authors.forename: Baidyanath
authors.initials: B
authors.lastname: Chakravarty
authors.forename: Lalji
authors.initials: L
authors.lastname: Singh
mesh_terms: D000293:Adolescent; D000328:Adult; D055430:Bone Morphogenetic Protein 15; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D055429:Growth Differentiation Factor 9; D006239:Haplotypes; D006801:Humans; D007194:India / Q000453:epidemiology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007621:Karyotyping; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D016649:Primary Ovarian Insufficiency / Q000453:epidemiology / Q000235:genetics*
chemical_list: C525901:BMP15 protein, human; D055430:Bone Morphogenetic Protein 15; C525897:GDF9 protein, human; D055429:Growth Differentiation Factor 9; D036341:Intercellular Signaling Peptides and Proteins