Rapid identification of a pathogenic variant of PROS1 in a thrombophilic family by whole exome sequencing

Abstract

Rationale: Venous 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 concerns: A thrombophilic family presented with multiple venous thrombosis was examined. Diagnoses: Molecular 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. Interventions: Whole 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. Outcomes: Using 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. Lessons: Our 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.

CRISPR Detection and Research on Screening Mutant Gene TTN of Moyamoya Disease Family Based on Whole Exome Sequencing

“…Screening family genetic patients to obtain new or known gene mutations, whole-exome sequencing has the advantages of accuracy and comprehension ( Zhang et al, 2021 ). However, whole-exome sequencing has drawbacks such as time-consuming and high cost, which is not conducive to the large-scale screening of samples.…”

“…Patients suffering from moyamoya disease generally could not heal themselves without scientific treatment, and even the condition may continue to aggravate, causing irreversible harm, and bringing great economic burdens to patients and their families to a certain extent (Zhang et al, 2022). Screening family genetic patients to obtain new or known gene mutations, whole-exome sequencing has the advantages of accuracy and comprehension (Zhang et al, 2021). However, whole-exome sequencing has drawbacks such as time-consuming and high cost, which is not conducive to the large-scale screening of samples.…”