Gene analysis of heterozygous protein C deficiency in a patient with pulmonary arterial thromboembolism

Abstract

A 16-yr-old male patient with heterozygous protein C deficiency developed acute pulmonary thromboembolism. The patient had low levels of plasma protein C antigen and activity (33 and 35% of normal, respectively). Analysis of the protein C gene by polymerase chain reaction (PCR) and direct sequencing revealed a nucleotide substitution (Arg169CGG----Trp169 TGG) in exon VII. This mutation is identical with protein C Tochigi, and the substituted amino acid is located at the cleavage site of the activation peptide of protein C. The mutant sequence was also detected in the mRNA transcripts of protein C gene. These results suggest that the possible mechanism of plasma protein C reduction is impaired stability or susceptibility to protein degradation during intracellular processing or after secretion into plasma. As this is a third independent case of protein C Tochigi with thromboembolism, the mutation of Arg169 (CGG) to Trp169 (TGG) in the protein C gene may be a "hot spot" and a common type of genetic lesion in congenital protein C deficiency with thromboembolic complications.