Characterization of plasminogen variants in healthy subjects and plasminogen mutants in patients with inherited plasminogen deficiency by isoelectric focusing gel electrophoresis

Katrin Tefs; Maria Georgieva; Stefan Seregard; Campbell R. Tait; Lori Luchtman-Jones; Maike Ziegler; Boris Hügle; Volker Schuster

doi:10.1160/TH04-01-0041

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(02): 352-357
DOI: 10.1160/TH04-01-0041

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Characterization of plasminogen variants in healthy subjects and plasminogen mutants in patients with inherited plasminogen deficiency by isoelectric focusing gel electrophoresis

Katrin Tefs

¹Children´s Hospital, University of Leipzig, Germany

,

Maria Georgieva

¹Children´s Hospital, University of Leipzig, Germany

,

Stefan Seregard

²Ophthalmic Pathology and Oncology Service, St Erik’s Eye Hospital and Karolinska Institute, Stockholm, Sweden

,

Campbell R. Tait

³Department of Haematology, Glasgow Royal Infirmary, UK

,

Lori Luchtman-Jones

⁴St. Louis Children’s Hospital, Washington University School of Medicine, St. Louis, Missouri, USA

,

Maike Ziegler

¹Children´s Hospital, University of Leipzig, Germany

,

Boris Hügle

¹Children´s Hospital, University of Leipzig, Germany

,

Volker Schuster

¹Children´s Hospital, University of Leipzig, Germany

› Author Affiliations

Abstract

Summary

Plasmin(ogen) plays an important role in fibrinolysis and wound healing. Severe hypoplasminogenemia has recently been linked to ligneous conjunctivitis. Plasminogen (plg) is known as a polymorphic protein and most of these variants have been identified using isoelectric focusing (IEF) gel electrophoresis. Here, we studied common plg variants from healthy subjects and plg mutants from three patients with hypoplasminogenemia and three subjects with dysplasminogenemia by molecular genetic analysis and IEF. Analysis of 24 healthy subjects showed that subjects with the most common IEF plg phenotype A (n = 12) were homozygous for aspartate at position 453 (453D), while both subjects with IEF plg phenotype B were homozygous for asparagine at this position (453N). Subjects with IEF plg phenotype AB (n = 10) were compound-heterozygous for 453D/453N. Three patients with severe hypoplasminogenemia and different plg gene mutations exhibited characteristic “abnormal” IEF band patterns when compared with IEF plg phenotypes A and B. In all heterozygous family members the observed IEF plg phenotype was derived from the wild type plg molecule only, probably due to low concentration of the mutant plg molecule in plasma. In contrast, in three unrelated subjects with heterozygous dysplasminogenemia an equal “mixture” of wild type and mutant plg was found by IEF analysis. In conclusion, plg phenotyping by IEF in combination with molecular analysis of the plg gene seems to be a useful method for characterization of plg variants and mutants.

Keywords

Isoelectric focusing (IEF) gel electrophoresis - plasminogen (plg) - hypoplasminogenemia - dysplasminogenemia - ligneous conjunctivitis

Full Text

References

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