title: Genetic diagnosis of dysplasminogenemia: detection of an Ala601-Thr mutation in 118 out of 125 families and identification of a new Asp676-Asn mutation.
abstract: Dysplasminogenemia (plasminogen abnormality) is frequently found in association with thrombosis. Two types of mutation, Ala601-Thr and Val355-Phe, have already been identified; the precise genetic defects of most of these patients, however, remain unknown. In this study, we examined the genetic DNAs of two unrelated cases by single-strand conformational polymorphism and nucleotide sequencing analysis. A new mutation, designated as Asp676-Asn, has been identified in these cases. This mutation leads to the loss of a negatively-charged residue and the creation of a potential carbohydrate attachment site, which may impair the enzymatic properties of plasminogen. As many as 158 individuals with dysplasminogenemia were analyzed by a combination of in vitro amplification and restriction digestion. Among 125 unrelated families, the Ala601-Thr mutation accounted for about 94% of cases. The Val355-Phe mutation was found in four unrelated families, indicating that it is a recurring mutation and is not very rare.
authors.affiliation: Department of Molecular Pathological Biochemistry, Yamagata University School of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tsutsumi
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: T
authors.initials: T
authors.lastname: Sakata
authors.forename: T
authors.initials: T
authors.lastname: Mlyata
authors.forename: A
authors.initials: A
authors.lastname: Ichinose
mesh_terms: D000328:Adult; D000409:Alanine / Q000737:chemistry*; D001216:Asparagine / Q000737:chemistry*; D001224:Aspartic Acid / Q000737:chemistry*; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008297:Male; D009154:Mutation; D010649:Phenylalanine / Q000737:chemistry; D010958:Plasminogen / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA; D013329:Structure-Activity Relationship; D013912:Threonine / Q000737:chemistry; D013927:Thrombosis / Q000209:etiology
chemical_list: D013912:Threonine; D001224:Aspartic Acid; D010649:Phenylalanine; D001216:Asparagine; D010958:Plasminogen; D000409:Alanine