Analysis of cerebral infarction caused by dysplasminogenemia in three pedigrees

Abstract

Background and aims: Dysplasminogenemia is a rare heritable disease caused by plasminogen (PLG) gene defects resulting in hypercoagulability. In this report we describe three notable cases of cerebral infarction (CI) complicated with dysplasminogenemia in young patients. Methods: Coagulation indices were examined on STAGO STA-R-MAX analyzer. PLG: A was analyzed using a chromogenic substrate-based approach using a chromogenic substrate method. All nineteen exons of PLG gene and their 5'and 3'flanking regions were amplified by Polymerase chain reaction (PCR). Suspected mutation was confirmed by reverse sequencing. Results: PLG activity (PLG:A) in proband 1 and 3 of his tested family members, proband 2 and 2 of his tested family members, and proband 3 and her father were all reduced to roughly 50% of normal levels. Sequencing led to the identification of a heterozygous c.1858G>A missense mutation in exon 15 of the PLG gene in these three patients and affected family members. Conclusion: We conclude that the observed reduction in PLG:A was the result of this p.Ala620Thr missense mutation in the PLG gene. The CI incidence in these probands may be attributable to the inhibition of normal fibrinolytic activity as a consequence of this heterozygous mutation.

Keywords: dysplasminogenemia; genetic mutations; heredity; juvenile stroke; plasminogen.

FIGURE 1

Brain imaging findings of hereditary abnormal plasminogen patients [proband 1: (A,B); proband 2: (C,D); proband 3: (E,F)]. (A,B): Diffusion weighted imaging (DWI) and T2 sequence respectively showed acute infarction in left paraventricular; (C,D): DWI and T2 respectively showed acute infarction in right pons; (E,F): DWI, T2 sequence, respectively showed acute infarction in the right frontal lobe.

FIGURE 2

The sequencing results of plasminogen gene in exon 15 of hereditary plasminogen deficiency patients. (A–C): the gene sequencing results of probands 1, 2 and 3, respectively, and the heterozygous mutation site c.1858G > (A) is shown by the arrow. (D) is the gene sequencing result of the wild type.