title: Mutational analysis of the betaglycan gene-coding region in susceptibility for ovarian failure.
abstract: BACKGROUND
  Elevation of FSH is frequently a consequence of impaired ovarian follicle growth. Down-regulation of the FSH levels by inhibins is mediated through its receptor betaglycan in the gonadotrophs. Understanding of germline status of the betaglycan gene (TGFBR3) is essential for ovarian failure pathophysiology.
  
  
  METHODS
  Sequence analysis was performed for the coding region of TGFBR3 gene in a cohort of 196 ovarian failure cases that include 133 premature ovarian failure (POF) cases, 63 primary amenorrhoea (PA) cases compared with 200 controls.
  
  
  RESULTS
  Forty-six variants including six novel exonic variants and 16 novel intronic variants were revealed. Two variants were missense: (i) p.Iso184Val in a control and (ii) p.Pro775Ser in a POF case. Genotypic distribution of three variants (c.382-81C>T, c.382-77T>C and c.1200G>A) was significantly different in the patients as compared with the controls. Five variants c.382-81C>T, c.382-77T>C, c.566-216G>A, c.1200G>A and c.2022T>C were chosen for haplotyping. The CCAAT haplotype was significantly higher in the patient population as compared with the controls (P = 0.00007).
  
  
  CONCLUSIONS
  This study establishes the first mutational report of the TGFBR3 gene in correlation with ovarian failure. Significant diversity of genotype distribution and haplotype analysis suggested susceptibility of the TGFBR3 gene for ovarian failure aetiology.
authors.affiliation: Centre for Cellular and Molecular Biology, Hyderabad, India.
authors.forename: H
authors.initials: H
authors.lastname: Dixit
authors.forename: K L
authors.initials: KL
authors.lastname: Rao
authors.forename: V V
authors.initials: VV
authors.lastname: Padmalatha
authors.forename: M
authors.initials: M
authors.lastname: Kanakavalli
authors.forename: M
authors.initials: M
authors.lastname: Deenadayal
authors.forename: N
authors.initials: N
authors.lastname: Gupta
authors.forename: B N
authors.initials: BN
authors.lastname: Chakrabarty
authors.forename: L
authors.initials: L
authors.lastname: Singh
mesh_terms: D000328:Adult; D000568:Amenorrhea / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D011509:Proteoglycans / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; C071736:betaglycan