Analysis of four hereditary protein C deficiencies associated with vascular thromboembolism

Abstract

To analyze the clinical features and gene mutations in four families with hereditary protein C (PC) de ciency and explore their association with vascular thromboembolism. MethodsThe clinical data of four patients with PC de ciency were retrospectively analyzed. Venous blood samples were collected from the four affected patients and their family members, and relevant coagulation indexes and thrombin production and inhibition tests were performed. PCR was used to amplify and directly sequence the PROC gene of the prevalent patients. Software analysis was conducted to assess the conservativeness and pathogenicity of the mutated loci. Protein models were constructed to analyze the spatial structure before and after the mutation. ResultsThrombin generation and inhibition assays demonstrated impaired anticoagulation in all four probands. Proband 1 and 4 presented clinically with pulmonary embolism and lower extremity deep vein thrombosis (DVT), Proband 2 with cerebral infarction, and Proband 3 with DVT. Genetic analysis revealed the presence of the following mutations: c541T > G heterozygous missense mutation, c.577-579delAAG heterozygous deletion mutation, c.247-248insCT heterozygous insertion mutation, c.659G > A heterozygous missense mutation, and a new variant locus c.1146_1146delT heterozygous deletion mutation in the four probands, respectively. Conservativity and pathogenicity analyses con rmed that most of these amino acid residues were conserved, and all the mutations were found to be pathogenic. Analysis of protein modeling revealed that these mutations induced structural alterations in the protein or led to the formation of truncated proteins. ConclusionThe identi ed mutations are likely associated with decreased PC levels in each of the four families. The clinical manifestations of hereditary PC de ciency exhibit considerable diversity.