title: A quantitative protein S deficiency associated with a novel nonsense mutation and markedly reduced levels of mutated mRNA.
abstract: A 50-year-old Japanese man who had experienced recurrent episodes of venous thrombosis was found to have a hereditary protein S deficiency. The amount of total protein S antigen in plasma was reduced by approximately 50% in the patient and his two sons. DNA sequence analysis revealed a novel nonsense mutation, TAG for Gln 522 (CAG), in exon 14 of the protein S gene. Family studies performed by mutagenic PCR followed by restriction enzyme digestion showed that the proband and his two sons were heterozygous for this mutation. An mRNA-based analysis indicated that transcripts of the mutated allele were markedly reduced in the platelets of the affected individuals. Immunoblot analysis failed to detect the truncated mutant of protein S in the plasma or platelets of affected members. Our results demonstrated that this novel nonsense mutation was responsible for the quantitative deficiency of protein S.
authors.affiliation: First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamazaki
authors.forename: M
authors.initials: M
authors.lastname: Hamaguchi
authors.forename: A
authors.initials: A
authors.lastname: Katsumi
authors.forename: K
authors.initials: K
authors.lastname: Kagami
authors.forename: T
authors.initials: T
authors.lastname: Kojima
authors.forename: J
authors.initials: J
authors.lastname: Takamatsu
authors.forename: H
authors.initials: H
authors.lastname: Saito
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001792:Blood Platelets / Q000737:chemistry; D003169:Complement Inactivator Proteins; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017293:Protein S / Q000235:genetics*; D018455:Protein S Deficiency / Q000150:complications / Q000235:genetics*; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics*; D011951:Receptors, Complement / Q000032:analysis; D012008:Recurrence; D013924:Thrombophlebitis / Q000235:genetics* / Q000517:prevention & control; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D017293:Protein S; D012333:RNA, Messenger; D011951:Receptors, Complement; D014859:Warfarin