Analysis of cerebral infarction due to inherited dysplasminogenemia / 中华神经科杂志

ABSTRACT

Objective:To investigate the relationship between inherited dysplasminogenemia and cerebral infarction (CI) by phenotype and gene mutation analysis of 2 inherited dysplasminogenemia pedigrees.Methods:Retrospective analysis was carried out on clinical data of 2 patients diagnosed with CI who were treated in the Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University in January and March 2021, and peripheral venous blood samples were collected from proband 1 and his family members (8 subjects, 4 generations in total) and proband 2 and her family members (5 subjects of 3 generations in total), and their plasminogen (PLG) activity (PLGA), protein C activity, protein S activity, antithrombin activity and the content of PLG antigen (PLG Ag), fibrinogen, D-dimer and fibrinogen degradation products were measured for definite diagnosis. All 19 exons,5′ and 3′ untranslated regions of PLG were amplified with polymerase chain reaction, and the amplification products were analyzed by direct DNA sequencing. The results were compared with human PLG reference sequences published in the National Center for Biotechnology Information database using Chromas software to find the mutation sites, and confirmed by reverse sequencing.Results:Both of the 2 patients with confirmed CI had a young onset, and PLG A was reduced to 21% in the proband 1 and to about 50% in 4 family members; PLG A was reduced to about 50% in the proband 2 and 2 family members; PLGAg and the above tests were essentially normal in both probands and family members. Gene analysis showed that the proband 1 had the homozygous mutation of c.1858G>A in exon 15, the 4 family members of the proband 1, proband 2 and her 2 family members had the heterozygous mutation of c.1858G>A in exon 15, which resulted in a mutation of alanine at position 620 in PLG to threonine (p.Ala620Thr).Conclusions:The decrease of PLGA was caused by the p.Ala620Thr missense mutation of PLG gene. Proband having CI may be related to the inhibition of fibrinolytic function in the organism due to the p.Ala620Thr missense mutation.