title: BMP15 and GDF9 Gene Mutations in Premature Ovarian Failure.
abstract: BACKGROUND
  Premature ovarian failure (POF) is an ovarian defect characterized by the premature depletion of ovarian follicles before the age of 40, representing one major cause of female infertility. Mutations in bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) have been shown to be associated with POF.
  
  
  METHODS
  Genomic DNA was isolated from 52 idiopathic premature ovarian failure patients and 100 normal control individuals. Exons of BMP15 and GDF9 gene were amplified using PCR method and subjected to directed sequencing. Variants were identified by comparing the sequences obtained with normal sequences from NCBI database.
  
  
  RESULTS
  Four BMP15 gene variants were identified in 6 patients in heterozygous condition. Out of these 4 variants, 3 variants namely, c.165A>T (p.Glu55Asp), c.538 G>T (p.Aln180 Ser) and c. 510_512 delT were novel variants. In silico analysis using SIFT, Provean and Polyphen 2 score predicted the non-deleterious effect of c.165A>T and c.538 G>T variant. 788insTCT variant was identified in 3 patients. No variant was identified in GDF9 gene in any patients and controls.
  
  
  CONCLUSIONS
  Although the variant has been identified in BMP15 gene but it may not be associated with the premature ovarian failure.
authors.affiliation: Central Research Laboratory, Sri Aurobindo Medical College and PG Institute, Indore, India.
authors.forename: Ravindra
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Obstetrics & Gynaecology, Sri Aurobindo Medical College and PG Institute, Indore, India.
authors.forename: Madhuri
authors.initials: M
authors.lastname: Alwani
authors.affiliation: Central Research Laboratory, Sri Aurobindo Medical College and PG Institute, Indore, India.
authors.forename: Susmit
authors.initials: S
authors.lastname: Kosta
authors.affiliation: Department of Obstetrics & Gynaecology, Sri Aurobindo Medical College and PG Institute, Indore, India.
authors.forename: Ravjyot
authors.initials: R
authors.lastname: Kaur
authors.affiliation: Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Sarita
authors.initials: S
authors.lastname: Agarwal
keywords: Bone morphogenetic protein 15; Female infertility; Gene mutation; Growth differentiation factor 9; Premature ovarian failure