title: Detection of two missense mutations and characterization of a repeat polymorphism in the factor VII gene (F7).
abstract: The 3' portion of the coagulation factor VII gene, containing the activation and serine protease domains, was investigated in four subjects with factor VII deficiency by temperature gradient gel electrophoresis and sequencing of polymerase chain reaction (PCR) products. Molecules displaying an altered melting behaviour were detected in three subjects, and direct sequencing showed two mutations. A G-to-T transversion causing a missense mutation, Cys-310 to Phe, suppresses a disulphide bond conserved in the catalytic domain of all serine proteases. This mutation, which in the homozygous form causes a severe reduction in protease activity (4%), was found in two patients from different Italian regions. A G-to-A transition, which gives rise to a missense mutation, Arg-304 to Gln, and is associated with the factor VII padua variant, was found in the heterozygous form in a subject also affected by von Willebrand disease. Two polymorphic alleles, which differ in one repeat monomer element, were precisely mapped in a region spanning the exon-intron 7 border of the factor VII gene and studied in families with factor VII or X deficiency.
authors.affiliation: Centro Studi Biochimici delle Patologie del Genoma Umano, Instituto di Chimica Biologica, Ferrara, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Marchetti
authors.forename: P
authors.initials: P
authors.lastname: Patracchini
authors.forename: D
authors.initials: D
authors.lastname: Gemmati
authors.forename: V
authors.initials: V
authors.lastname: DeRosa
authors.forename: M
authors.initials: M
authors.lastname: Pinotti
authors.forename: G
authors.initials: G
authors.lastname: Rodorigo
authors.forename: A
authors.initials: A
authors.lastname: Casonato
authors.forename: A
authors.initials: A
authors.lastname: Girolami
authors.forename: F
authors.initials: F
authors.lastname: Bernardi
mesh_terms: D001483:Base Sequence; D002648:Child; D002869:Chromosome Aberrations; D002882:Chromosomes, Human, Pair 13; D004252:DNA Mutational Analysis; D005167:Factor VII / Q000235:genetics*; D005168:Factor VII Deficiency / Q000235:genetics*; D005171:Factor X Deficiency / Q000235:genetics; D005260:Female; D005796:Genes / Q000235:genetics*; D005973:Glutamine; D006801:Humans; D007558:Italy; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D005973:Glutamine; D005167:Factor VII