CHEN Huilin,WANG Sheng,YANG Ting, et al. Clinical features and genotype analysis of two pedigrees with hereditary protein C deficiency[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2024, 54(10): 811-816.
Abstract：Objective: To investigate the clinical features and gene mutations in two families with hereditary protein C (PC) deficiency, and to explore the relationship between PC deficiency and vascular thromboembolism.Methods: Peripheral blood and clinical data were collected from two probands and their family members (eleven people across three generations), and the PC activity, protein S activity and antithrombin activity were detected to confirm the phenotypic diagnosis. PCR was used to amplify and directly sequence the PROC gene of the probands.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. Results: The clinical manifestations of proband 1 were pulmonary embolism and deep venous thrombosis of the lower extremities, and proband 2 had DVT. Genetic analysis revealed that the proband 1 had c.541T>G heterozygous missense mutation and c.577-579delAAG heterozygous deletion mutation and the proband 2 had a c.659G>A heterozygous missense mutation. Conservativeness and pathogenicity analysis confirmed that most of these amino acid residues were conserved, and all the mutations were found to be pathogenic. Protein models showed that most of these mutations caused changes in the hydrogen bonds between amino acids and side-chain groups or produced truncated proteins.Conclusion: The c.541T>G heterozygous missense mutation, c.577-579delAAG heterozygous deletion mutation and c.659G>A heterozygous missense mutation were related, respectively, to the decrease of PC level in these two probands, and these mutations may also be one of the reasons for the occurrence of VTE.
