Two Novel Variants in the Protein S Gene PROS1 Are Associated with Protein S Deficiency and Thrombophilia

Acta Haematol. 2021;144(2):222-226. doi: 10.1159/000508525. Epub 2020 Jul 10.

Abstract

Protein S (PS) is an important anticoagulant. Its main function is to act as a non-enzymatical cofactor of activated protein C. PS deficiency is defined as low plasma levels of PS and/or loss of function associated with variable risk of venous thromboembolism (VTE). We report 2 novel variants in the PS gene (PROS1) which are associated with PS deficiency and severe thrombophilic diathesis in 2 patients. Patient 1 suffered from 3 VTE events, including a spontaneous VTE at the age of 19. Patient 2 suffered from 2 provoked VTE events. In both patients decreased plasma levels of PS antigen as well as decreased PS activity were found. Gene sequencing results showed a heterozygous deletion of 8 base pairs (c.938_945delTAAAATTT, p.Leu313Serfs13*) in exon 9 of the PROS1 gene in patient 1 and a missense variant (c.1613C>T, p.Ser538Phe) in patient 2. Due to the clinically proven history of recurrent VTE events in both patients, genetic testing of first-degree relatives is discussed.

Keywords: Protein S deficiency; Thrombophilia; Thrombosis; Venous thromboembolism.

Publication types

  • Case Reports

MeSH terms

  • Anticoagulants / therapeutic use
  • Exons
  • Factor V / genetics
  • Female
  • Gene Deletion
  • Heterozygote
  • Homozygote
  • Humans
  • Middle Aged
  • Mutation, Missense
  • Polymorphism, Single Nucleotide
  • Protein S / genetics*
  • Protein S Deficiency / complications
  • Protein S Deficiency / diagnosis*
  • Protein S Deficiency / genetics
  • Venous Thromboembolism / diagnosis*
  • Venous Thromboembolism / drug therapy
  • Venous Thromboembolism / etiology

Substances

  • Anticoagulants
  • PROS1 protein, human
  • Protein S
  • Factor V