Severe dysplasminogenemia due to homozygous PLG Ala620Thr variant in a Korean woman without a history of venous thromboembolism: A case report and literature review

Abstract

Rationale: Plasminogen plays an important role in fibrinolysis and is encoded by the PLG gene. The missense variant PLG Ala620Thr is the major cause of dysplasminogenemia in East Asian countries, including Korea. Although dysplasminogenemia was first reported in a Japanese patient with recurrent venous thromboembolism (VTE), subsequent studies have not demonstrated any clear association between the PLG Ala620Thr variant and the risk of VTE. To the best of our knowledge, this is the first report of a homozygous PLG Ala620Thr variant case from Korea.

Patient concerns: Here, we report a Korean family with PLG Ala620Thr mutation. The proband was a 34-year-old man who presented with multiple thrombotic arterial embolism and cardiac myxoma.

Interventions: Laboratory workup, including coagulation profile and PLG gene sequencing, was carried out for the affected family.

Diagnosis and outcome: The proband carried a heterozygous PLG Ala620Thr variant with decreased plasminogen activity of 65%. His 53-year-old mother, who had no reported history of VTE, was homozygous for the PLG Ala620Thr variant with decreased plasminogen activity of just 25%. Decreased plasminogen activity indicates dysplasminogenemia.

Lessons: We believe that this clinically silent homozygous case supports the previous findings that isolated PLG Ala620Thr variant does not confer a significant risk of VTE.

Figure 1

The pedigree of the proband family. The arrow indicates the proband and the filled symbol indicates subject with thrombosis. Below each symbol, the combination of amino acids and the percentage of the plasminogen activity are presented. A = alanine, T = threonine.

Figure 2

Sequencing analysis of the PLG gene. The proband and his sister were heterozygous whereas his mother was homozygous for c.1858G > A (p. Ala620Thr).