title: Three novel missense mutations in unrelated Japanese patients with type I and type II protein S deficiency and venous thrombosis.
abstract: A molecular analysis of protein S deficiency in three unrelated Japanese patients was performed. An approximately 50% reduction in both functional and immunologic levels of protein S was detected in the plasmas from two unrelated patients, designated protein S Osaka 1 and protein S Osaka 2. An approximately 50% reduction in the functional level, but a normal immunologic level of protein S, was detected in plasma from a third patient, designated protein S Osaka 3. All of the exons and exon/intron junctions of the protein S gene were studied using a strategy combining polymerase chain reaction amplification and rapid non-radioactive single-strand conformational polymorphism analysis. We identified a G-to-A change in exon X of the protein S gene in protein S Osaka 1. This mutation resulted in the substitution of Gly for Ser at position 295 in the sex hormone-binding globulin-like region. In protein S Osaka 2, a G-to-C change at the position of the 3' end of exon III was identified, leading to the amino acid substitution of Val46 by Leu in the aromatic stack region. In protein S Osaka 3, an A-to-G change in exon II was identified, leading to the substitution of Lys9 by Glu in the Gla domain. It was concluded that the Gly295-to-Ser mutation and Val46-to-Leu mutation cause type I protein S deficiency and that the Lys9-to-Glu mutation causes type II deficiency.
authors.affiliation: Department of Surgery II, Osaka University Medical School, Suita, Japan. hfujimur@surg2.med.osaka-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Fujimura
authors.forename: J
authors.initials: J
authors.lastname: Kambayashi
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Sakon
authors.forename: T
authors.initials: T
authors.lastname: Kawasaki
authors.forename: H
authors.initials: H
authors.lastname: Ariyoshi
authors.forename: E
authors.initials: E
authors.lastname: Suehisa
authors.forename: M
authors.initials: M
authors.lastname: Monden
authors.forename: T
authors.initials: T
authors.lastname: Miyata
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D005091:Exons; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017293:Protein S / Q000032:analysis / Q000235:genetics; D018455:Protein S Deficiency / Q000235:genetics*; D012307:Risk Factors; D013924:Thrombophlebitis / Q000235:genetics*
chemical_list: D017293:Protein S