A novel mutation Gly222Arg in PROS1 causing protein S deficiency in a patient with pulmonary embolism.

BACKGROUND: Thrombophilia is becoming a more frequently reported disorder these years. Hereditary protein S deficiency is one of the anticoagulant deficiencies that eventually results in thrombophilia.

CASE PRESENTATION: A 24-year-old male patient was suffering from unexplained thrombosis for the second time with a family history of deep venous thrombosis. Screening tests for anticoagulant proteins found the activity of protein S markedly lowered (5.0%). The patient was discharged after anticoagulation treatment. Four years later, the review still showed the activity of protein S in his plasma decreased (16.0%). Molecular genetic analysis revealed him homozygous for a missense mutation, c.664G>A, in the exon7 of PROS1. The mutation discovered here is the first mutation affecting the codon 222 of PROS1. This mutation results in the replacement of the glycine at the codon 222 of protein S with arginine, leading to a reduction of protein S function.

CONCLUSIONS: The finding of this mutation may help with the understanding of the mechanism of protein S deficiency, especially in the Chinese population.