Background: Hereditary Protein S deficiency is a rare disease characterized by reduced activity of protein S, a plasma serine protease that has a complex role in blood coagulation, inflammation and apoptosis.

Aims: To analyze the mutations of PROS1 gene and identify the potential correlation between genotype and phenotype.

Methods: We collected clinical data of 17 Protein S deficiency patients, analyzed mutations of PROS1 gene at the genomic DNA by the next generation sequencing (NGS), and further determined the potential correlation between genotype and phenotype.

Results: Of these 17 probands, 52.9% (9/17) experienced multi-site and/or recurrent thrombotic episodes, mainly manifested as deep venous thrombosis. Additional risk factors of VTE were observed in 41% (7/17) probands who exhibited a significantly higher rate of recurrent VTE compared with those not, in which 3 probands were complicated by anti-phospholipid syndrome. Most patients and family members exhibited quantitative Protein S deficiency with impairment of both activated protein C and tissue factor pathway inhibitor cofactor activities. A total of 15 unique mutations identified, including 8 novel mutations. Most mutations (11/15, 73%) were missense or nonsense mutations, whereas two frameshift mutations ( p.S194fs and p.N583fs) were located in exons 6 and 14 respectively, and one splcing mutation, c.1493-17T>C,  was located in Intron 12.

Conclusions: PROS1 gene analysis can make a definite diagnosis of Protein S deficiency and identify mutation carriers, and this research provides a framework for correlating the clinical pathogenesis of Protein S deficiency to genetic backgrounds in the Chinese population.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/clinical-and-molecular-characterization-of-chinese-patients-with-protein-s-deficiency/