title: Mutational analysis of the FIGLA gene in women with idiopathic premature ovarian failure.
abstract: OBJECTIVE
  The aim of our study was to identify the association of FIGLA (factor in the germ line α) gene variants with premature ovarian failure (POF) in the Indian population.
  
  
  METHODS
  Two hundred nineteen women with idiopathic POF and 230 healthy controls were recruited for this study. All exons, intron-exon boundaries, and untranslated regions of the FIGLA gene were analyzed by polymerase chain reaction and sequencing. All FIGLA variants were analyzed in silico, using PolyPhen, SIFT, MutationTaster, PMUT, I-Mutant, Mupro, Align-GVGD, PROVEAN, and HOPE software, to predict pathogenicity and changes in protein stability.
  
  
  RESULTS
  Seven different FIGLA variants were detected among women with POF. Two exon 3 variants, c.427G → C and c.557C → T, showed strong association between cases and controls (P = 0.02 and P = 0.02, respectively). Significant differences in both of these variants were observed between cases and controls in genotype and dominant models. No significant difference between controls and women with POF was found on haplotype analysis. A nonsynonymous variant, p.(Arg83Cys), was found only in POF cases. Variant p.(Arg83Cys) lies in the functional domain of the FIGLA gene (basic helix-loop-helix), and protein alignments reveal that it is highly conserved among mammals. In silico analysis suggests the functional involvement of p.(Arg83Cys) and p.(Ser141Thr) variants in POF pathogenesis.
  
  
  CONCLUSIONS
  We have established a strong association between FIGLA gene variants and POF in Indian women, which may be a potential genetic risk factor in the development of idiopathic POF. However, further independent genetic and functional studies are necessary to confirm our findings.
authors.affiliation: From the 1Biology Division, CSIR Indian Institute of Chemical Technology, Hyderabad, India; 2Department of Genetics, Osmania University, Hyderabad, India; and 3Infertility Institute and Research Center, Secunderabad, India.
authors.forename: Durgadatta
authors.initials: D
authors.lastname: Tosh
authors.forename: Hanumanth Surekha
authors.initials: HS
authors.lastname: Rani
authors.forename: Upadhyayula Suryanarayana
authors.initials: US
authors.lastname: Murty
authors.forename: Anupama
authors.initials: A
authors.lastname: Deenadayal
authors.forename: Paramjit
authors.initials: P
authors.lastname: Grover
mesh_terms: D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D003198:Computer Simulation; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007194:India; D015810:Linkage Disequilibrium; D058011:Multifactor Dimensionality Reduction; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D016649:Primary Ovarian Insufficiency / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005640:Follicle Stimulating Hormone; C539077:FIGLA protein, human