title: Isoelectric focusing pattern of plasminogen mutants of patients with hypoplasminogenemia: correlation of in-vitro data with computer-predicted isoelectric points (pI).
abstract: Plasminogen (plg), the circulating proenzyme of plasmin in blood, is a polymorphic protein and most of these natural variants have been identified using isoelectric focusing (IEF) gel electrophoresis. Here, we show that a rare plg gene polymorphism 504R/W is associated with IEF phenotype A3 on the protein level. One healthy individual with homozygous plg gene polymorphism 504W studied so far exhibited low normal plg antigen and slightly decreased plg activity, suggesting that this polymorphism is associated with (mild) hypoplasminogenemia. In addition, we present the findings of IEF phenotyping of plg mutants of 26 patients with severe hypoplasminogenemia, showing one of the following four IEF patterns: A3-like, A3A-like, B-like and AB-like. In the plasma of most compound heterozygous patients, only one of the two plg mutants was detectable by IEF electrophoresis, probably due to undetectable plasma concentration of the 2nd plg mutant. In almost all cases, pI of plg mutants and variants predicted by computer modeling were in good agreement with the observed IEF band pattern. plg phenotyping by IEF in combination with molecular genetic analysis of the plg gene is a useful approach to characterize plg mutants and variants further.
authors.affiliation: Hospital for Children and Adolescents, University of Leipzig, Liebigstrasse 20a, Leipzig, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Tefs
authors.forename: Maria
authors.initials: M
authors.lastname: Ott-Gueorguieva
authors.forename: Louise
authors.initials: L
authors.lastname: Kobelt
authors.forename: Maike
authors.initials: M
authors.lastname: Ziegler
authors.forename: Christian
authors.initials: C
authors.lastname: Hintze
authors.forename: Boris
authors.initials: B
authors.lastname: Hügle
authors.forename: Volker
authors.initials: V
authors.lastname: Schuster
mesh_terms: D000465:Algorithms; D000483:Alleles; D001778:Blood Coagulation Disorders / Q000175:diagnosis / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency; D006720:Homozygote; D006801:Humans; D007525:Isoelectric Focusing / Q000379:methods*; D007526:Isoelectric Point; D008297:Male; D058889:Molecular Typing / Q000379:methods*; D010290:Parents; D010641:Phenotype; D010958:Plasminogen / Q000737:chemistry / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics*; D017422:Sequence Analysis, DNA; D035781:Siblings; D012984:Software
chemical_list: D020033:Protein Isoforms; D010958:Plasminogen