title: Factor VIII gene analysis in Japanese CRM-positive and CRM-reduced haemophilia A patients by single-strand conformation polymorphism.
abstract: Haemophilia A is the most common X-linked blood coagulation disorder; it is caused by deficiency of factor VIII activity (FVIII:C). Half of the affected patients do not have detectable levels of FVIII protein in their plasma, whereas about 5% have normal levels of the FVIII antigen (FVIII:Ag) (> 50 u/dl), and are called cross-reacting material (CRM) positive (CRM+ or A+). About 45% of patients have reduced levels of the FVIII:Ag (1-50 u/dl), classified as CRM reduced (CRM[R] or A[R]). We screened the FVIII gene of 13 Japanese patients (five CRM+ and eight CRM[R]) by single-strand conformation polymorphism, and identified 11 different mutations in 13 patients by analysing all 26 exons (Trp255Cys, Tyr473Cys, Gly479Arg, Arg531His, Thr667Arg, Arg1689Cys, Arg1941Gln, Arg2150His, Arg2159Cys, Thr2245Ala and Gly2285Val). Seven mutations were identified in the A domains (four in the A2 domain). All the mutations are point mutations resulting in missense codons. Four mutations (Trp255Cys, Thr667Arg, Thr2245Ala and Gly2285Val) have not been described previously.
authors.affiliation: Department of Paediatrics, Nara Medical University, Kashihara City, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Morichika
authors.forename: M
authors.initials: M
authors.lastname: Shima
authors.forename: S
authors.initials: S
authors.lastname: Kamisue
authors.forename: I
authors.initials: I
authors.lastname: Tanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Imanaka
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Shibata
authors.forename: S
authors.initials: S
authors.lastname: Pemberton
authors.forename: K
authors.initials: K
authors.lastname: Gale
authors.forename: J
authors.initials: J
authors.lastname: McVey
authors.forename: E G
authors.initials: EG
authors.lastname: Tuddenham
authors.forename: A
authors.initials: A
authors.lastname: Yoshioka
mesh_terms: D004797:Enzyme-Linked Immunosorbent Assay; D005169:Factor VIII / Q000235:genetics*; D006467:Hemophilia A / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D005169:Factor VIII