title: Factor VIII Antigen, Activity, and Mutations in Hemophilia A.
abstract: Factor VIII (FVIII) activity, antigen, and its gene mutation in patients may give us some insight into structure-activity relationship and probable reason for its low level in a particular patient. A total of 53 cases with hemophilia A and 17 normal individuals were analyzed for
  C and
  Ag levels along with their blood groups to determine their cross-reacting material (CRM) status. In all, 37 cases (18 moderate and 19 mild) were found to have discordant CRM status. Missense mutations (Ala723ThrandLys439Ser) and protein truncating changes (Trp1854*andArg2326*) were observed in 2 each of these cases. Although 37 (70%) of the 53 had discordant antigen-activity ratio, majority of those mutations produced FVIII with low FVIII-specific activity. However, 4 (7.5%) of the 53 mutations produced higher specific activity of FVIII. It is possible that these mutations either produce a secretory defect or an increased metabolic turnover to account for the low levels of FVIII with these mutations.
authors.affiliation: Department of Thrombosis Haemostasis, National Institute of Immunohaematology (ICMR), Mumbai, Maharashtra, India.
authors.forename: Preethi S
authors.initials: PS
authors.lastname: Nair
authors.affiliation: Department of Thrombosis Haemostasis, National Institute of Immunohaematology (ICMR), Mumbai, Maharashtra, India.
authors.forename: Shrimati
authors.initials: S
authors.lastname: Shetty
authors.affiliation: Department of Thrombosis Haemostasis, National Institute of Immunohaematology (ICMR), Mumbai, Maharashtra, India kanjakshaghosh@hotmail.com.
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
mesh_terms: D019943:Amino Acid Substitution; D018389:Codon, Nonsense; D005169:Factor VIII / Q000235:genetics / Q000378:metabolism; D006467:Hemophilia A / Q000097:blood / Q000235:genetics; D006801:Humans; D008297:Male; D020125:Mutation, Missense
chemical_list: D018389:Codon, Nonsense; C078147:F8 protein, human; D005169:Factor VIII
keywords: cross-reacting material; hemophilia A; mutations