• Wenwen Zhang, Chen Huang, and Wei Zhou.
• Department of Vascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
• Medicine (Baltimore). 2021 Dec 30; 100 (52): e28436e28436.

RationaleVenous thrombosis remains a significant problem in modern days. Genetic factors contribute to a subset of patients with venous thrombosis. It is sometimes challenging to identify the underlying culprit in thrombophilic individuals based on traditional laboratory testing and Sanger sequencing.Patient ConcernsA thrombophilic family presented with multiple venous thrombosis was examined.DiagnosesMolecular genetic analysis revealed a pathogenic missense variant of the PROS1 gene. Based on this finding and clinical manifestations, a final diagnosis of protein S deficiency was made.InterventionsWhole exome sequencing (WES) of the proband was performed to identify disease-causing variants. Subsequently, Sanger sequencing was performed to validate the variant in the affected members.OutcomesUsing WES, we rapidly identified a proven pathogenic missense variant (c.1543C > T, p.Arg515Cys) in the sex hormone-binding globulin domain of PROS1, which was confirmed by Sanger sequencing. The decreased level and activity of protein S caused by the variant explained the phenotypes of the family. Patients received rivaroxaban as a long-term anticoagulation therapy and achieved a good prognosis.LessonsOur study suggests WES as a rapid search strategy to identify the genetic factors underlying thrombophilic disorders. Patients with venous thrombosis caused by PROS1 mutations could receive rivaroxaban as the first choice of anticoagulation therapy.Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.

29 keywords...

hide…