title: Phenotypic and genotypic characterization of Factor VII deficiency patients from Western India.
abstract: BACKGROUND
  Congenital factor VII (FVII) deficiency is a rare coagulation deficiency caused due to defects in the FVII gene.
  
  
  METHODS
  We analyzed 14 unrelated Indian patients with congenital FVII deficiency for mutations in FVII gene by conformation sensitive gel electrophoresis (CSGE) followed by DNA sequencing.
  
  
  RESULTS
  A total of 11 different missense mutations were identified, of which 5 were novel (Ala191Pro, Asp338Glu, Ile138Thr, Leu263Arg and Trp284Arg) and 6 had been previously reported (Cys22Arg, Arg152Gln, Cys310Phe, Thr324Met, Gly117Arg and His348Arg). Six of the 11 mutations were located in the catalytic serine protease domain, 3 in the activation domain and 1 each in the Gla and the second epidermal growth factor domain respectively. Multiple sequence alignment using ClustalW2 analysis showed that all the mutations were found in residues that are highly conserved across species. Implications of mutations on the structural stability and function of human factor VIII (hFVII) using Swiss-Pdb Viewer and the intra-molecular interactions of the mutant residues using PIC showed that there is a structural instability in all the mutants either by steric hindrance or instability in the protein molecule folding.
  
  
  CONCLUSIONS
  A wide spectrum of mutations was detected in the FVII gene; the presence of 6 out of 11 mutations in the serine protease domain suggests the crucial role of catalytic domain in FVII functional activity.
authors.affiliation: National Institute of Immunohaematology, 13th floor of KEM Hospital Campus, Parel, Mumbai, 400012, India.
authors.forename: Leenam
authors.initials: L
authors.lastname: Mota
authors.forename: Shrimati
authors.initials: S
authors.lastname: Shetty
authors.forename: Susan
authors.initials: S
authors.lastname: Idicula-Thomas
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001777:Blood Coagulation / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D017124:Conserved Sequence; D005167:Factor VII / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005168:Factor VII Deficiency / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D007194:India; D007223:Infant; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D055550:Protein Stability; D055815:Young Adult
chemical_list: D005167:Factor VII