不同家系遗传性蛋白C缺陷症12例临床表型和基因突变分析

OBJECTIVE: To investigate the molecular pathogenesis and clinical features of unrelated 12 patients with inherited coagulation protein C（PC）deficiency in Chinese population. METHODS: The PC activity（PC:A）and PC antigen（PC:Ag）were detected by chromogenic substrate and enzyme linked immunosorbent assay, respectively. The nine exons and flanking sequences of the protein C（PROC）gene were amplified by polymerase chain reaction with direct sequencing, and the suspected mutations were validated by reverse sequencing（clone sequencing for deletion mutations）. RESULTS: The PC:A of the 12 probands decreased significantly, ranging from 18% to 55%, and the PC:Ag of the 10 probands decreased significantly. Eleven mutations were found, out of which four mutations［c.383G>A（p.Gly128Asp）, c.997G>A（p.Ala291Thr）, c.1318C>T（p.Arg398Cys）, and c.532G>C（p.Leu278Pro）］were discovered for the first time. Six mutations were in the serine protease domain, four mutations were located in epidermal growth factor（EGF）-like domains, and one mutation was located in activation peptide. There were two deletion mutations（p.Met364Trp fsX15 and p.Lys192del）, and the rest were missense mutations. Mutations p.Phe181Val and p.Arg189Trp were identified in three unrelated families. All mutations may be inherited, and consanguineous marriages were reported in two families. Among the probands, nine cases had venous thrombosis, two cases had poor pregnancy manifestations, and one case had purpura. CONCLUSION: Patients with PC deficiency caused by PROC gene defects are prone to venous thrombosis, especially when there are other thrombotic factors present at the same time.