title: Detection and characterisation of two missense mutations at a cleavage site in the factor VIII light chain.
abstract: Haemophilia A is an X-linked bleeding disorder caused by a deficiency of factor VIII. As an essential cofactor in the intrinsic clotting cascade, factor VIII is activated and subsequently inactivated by proteolytic cleavages involving factor IIa (thrombin), factor Xa and activated protein C (APC). Investigation of the thrombin cleavage sites at amino acids 372 and 1689 of the factor VIII protein by oligonucleotide screening, DNA amplification and direct sequencing, enabled us to identify two missense mutations in 441 unrelated haemophiliacs. A C-to-T transition, which leads to the substitution of cysteine for arginine at position 1689, was found in a severely affected patient and a previously undescribed G-to-A substitution, causing replacement of arginine1689 with histidine, was found in a patient with mild disease.
authors.affiliation: Institute of Experimental Haematology and Blood Transfusion, Bonn, FRG.
authors.forename: R
authors.initials: R
authors.lastname: Schwaab
authors.forename: M
authors.initials: M
authors.lastname: Ludwig
authors.forename: L
authors.initials: L
authors.lastname: Kochhan
authors.forename: J
authors.initials: J
authors.lastname: Oldenburg
authors.forename: J H
authors.initials: JH
authors.lastname: McVey
authors.forename: H
authors.initials: H
authors.lastname: Egli
authors.forename: H H
authors.initials: HH
authors.lastname: Brackmann
authors.forename: K
authors.initials: K
authors.lastname: Olek
mesh_terms: D001483:Base Sequence; D015139:Blotting, Southern; D004247:DNA; D004252:DNA Mutational Analysis; D004262:DNA Restriction Enzymes; D005169:Factor VIII / Q000235:genetics*; D005819:Genetic Markers; D006467:Hemophilia A / Q000145:classification / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics* / Q000502:physiology; D015345:Oligonucleotide Probes; D015183:Restriction Mapping
chemical_list: D005819:Genetic Markers; D015345:Oligonucleotide Probes; D005169:Factor VIII; D004247:DNA; D004262:DNA Restriction Enzymes