Phenotypic and genotypic characterization of Factor VII deficiency patients from Western India
| Autor: | Shrimati Shetty, Kanjaksha Ghosh, Leenam Mota, Susan Idicula-Thomas |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Models Molecular Adolescent Protein Conformation Factor VII Deficiency Molecular Sequence Data Clinical Biochemistry Mutant India medicine.disease_cause Biochemistry Conserved sequence Young Adult chemistry.chemical_compound Asian People hemic and lymphatic diseases Genotype medicine Humans Missense mutation Amino Acid Sequence cardiovascular diseases Child Blood Coagulation Gene Conserved Sequence Genetics Serine protease Mutation Polymorphism Genetic biology Factor VII Protein Stability Biochemistry (medical) Infant General Medicine Middle Aged Phenotype Haplotypes chemistry Child Preschool biology.protein Female |
| Zdroj: | Clinica Chimica Acta. 409:106-111 |
| ISSN: | 0009-8981 |
| DOI: | 10.1016/j.cca.2009.09.007 |
| Popis: | 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. Conclusion 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. |
| Databáze: | OpenAIRE |
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