title: Five novel mutations of the protein S active gene (PROS 1) in 8 Norman families.
abstract: To further elucidate the molecular basis for hereditary thrombophilia, we screened the protein S active gene in 11 families with type I deficiency, using a strategy based on denaturing gradient gel electrophoresis (DGGE) of all the coding sequences. Fragments with an abnormal DGGE pattern were sequenced, and 5 novel mutations were identified in 8 families. The mutations were a 7-nucleotide deletion in exon II, a 4-nucleotide deletion in exon III, a T insertion in exon VII, a C to T transition transforming Leu 259 into Pro and a T to C transition transforming Cys 625 into Arg in 4 families. These mutations were the only sequence variations found in the propositus' gene exons and co-segregated with the plasma phenotype. A total of 28 members of these 8 families were heterozygous for one of the 5 mutations. Twenty-four (58,5%) of the 41 deficient subjects over 18 years of age had clinical thrombophilia, whereas the 13 subjects under 18 were asymptomatic. Of the 28 subjects, 6 (21,5%) were also found to bear the factor V Arg 506 Gln mutation.
authors.affiliation: INSERM U 428, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Duchemin
authors.forename: J Y
authors.initials: JY
authors.lastname: Borg
authors.forename: D
authors.initials: D
authors.lastname: Borgel
authors.forename: M
authors.initials: M
authors.lastname: Vasse
authors.forename: H
authors.initials: H
authors.lastname: Lévèque
authors.forename: M
authors.initials: M
authors.lastname: Aiach
authors.forename: S
authors.initials: S
authors.lastname: Gandrille
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002648:Child; D004247:DNA / Q000235:genetics*; D005602:France; D005820:Genetic Testing / Q000379:methods*; D016678:Genome; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D018455:Protein S Deficiency / Q000235:genetics*; D013927:Thrombosis / Q000235:genetics*
chemical_list: D004247:DNA