Gene diagnosis of seven patients with hereditary protein S deficiencies

Background: Hereditary protein S (PS) and protein C (PC) deficiencies are caused by gene mutations. The present research aimed to determine gene mutation sites in patients with thrombosis due to protein S deficiencies combined or not combined with protein C deficiencies. Methods: Patients with protein S deficiencies were enrolled. DNA was extracted from peripheral blood samples from these patients. All exons and their flanks of protein S genes (PROS) were amplified by polymerase chain reaction (PCR). After purification, the PCR products were sequenced directly and blastered to normal sequences, seeking out gene mutation sites. Polymorphism analysis was conducted by detecting the certain mutation in 50 normal people. Results: Seven patients were enrolled with thrombosis. They were diagnosed of protein S deficiencies combined or not combined with deficiencies of protein C. Polymorphism site G68395T on exon4 was identified in all seven patients. Non-sense mutation C68430T on exon4 was identified in patients No. 2 and No. 5. Missense mutation C86066T on exon10 was identified in patient No. 2. Missense mutation G82512C on exon9 was identified in patient No. 3. Searching PubMed, C86066T had been reported previously in a Hong Kong study, while C68430T and G82512C on PROS were the first ones reported worldwide. Conclusion: Polymorphism site G68395T and missense mutation C68430T, C86066T, and G82512C on PROS were identified and may be related to deficiencies of protein S. C68430T and G82512C were reported worldwide.