A pedigree analysis of pulmonary embolism caused by compound heterozygous mutations of protein C / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To study the molecular pathogenesis of protein C (PC) deficiency in a patient with pulmonary embolism and in his family members.</p><p><b>METHODS</b>Anticoagulated blood samples were collected from the proband and his family members to detect PC, PS and AT activities. PC antigen level was measured using ELISA. The genomic DNA was extracted to amplify all the 9 exons and their flanking sequences of PC gene using PCR, and the PCR products were sequenced. The mutated exons identified were amplified and sequenced for the other family members.</p><p><b>RESULTS</b>The proband and his parents and sister were identified as carriers of PC gene mutation, which led to type II PC deficiency. Sequencing of the proband's PC gene showed two heterozygous point mutations in exon 3 (G5540A) and exon 7 (C10230T) to cause compound heterozygous mutations of PC E29K and PC R147W, which were inherited from his father and mother, respectively. His sister was a heterozygote of PC R147W.</p><p><b>CONCLUSION</b>The proband is a compourd heterozygous mutations carrier of PC E29K and PC147W. PC E29K is a novel PC mutation, and PC R147W is a reported PC gene mutation seen in patients with type II hereditary PC deficiency and recurrent thrombosis.</p>