Three novel missense mutations in unrelated Japanese patients with type I and type II protein S deficiency and venous thrombosis.
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.
Fujimura
H
H
Department of Surgery II, Osaka University Medical School, Suita, Japan. hfujimur@surg2.med.osaka-u.ac.jp
Kambayashi
J
J
Kato
H
H
Sakon
M
M
Kawasaki
T
T
Ariyoshi
H
H
Suehisa
E
E
Monden
M
M
Miyata
T
T
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*
D017293:Protein S