PB0963 - Massive Parallel Sequencing-based Genetic Characterization of Korean Patients with Venous Thromboembolism

Monday, June 24, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Chang-Hun Park, MD, PhD

Associate Professor
Soon Chun Hyang University Hospital Bucheon
Bucheon, Kyonggi-do, Republic of Korea

Co-Author(s)

BK

Boram Kim

MD
Samsung medical cencer
Seoul, Seoul-t'ukpyolsi, Republic of Korea
KL

Ki-O Lee

BS
Samsung medical cencer
Seoul, Seoul-t'ukpyolsi, Republic of Korea
WK

Woochan Kwon

MD
Samsung medical cencer
Seoul, Seoul-t'ukpyolsi, Republic of Korea
TP

Taek Kyu Park

MD, PhD
Samsung medical cencer
Seoul, Seoul-t'ukpyolsi, Republic of Korea
SC

Sung-A Chang

MD, PhD
Samsung medical cencer
Seoul, Seoul-t'ukpyolsi, Republic of Korea
DK

Duk-Kyung Kim

MD, PhD
Samsung Changwon Hospital
Changwon, Kyongsang-namdo, Republic of Korea
SK

Sun-Hee Kim

MD, PhD
Samsung medical cencer
Seoul, Seoul-t'ukpyolsi, Republic of Korea
HK

Hee-Jin Kim

MD, PhD
Samsung medical cencer
Seoul, Seoul-t'ukpyolsi, Republic of Korea

Background: Genetic thrombophilia (GT) is a genetic condition that increases the risk of venous thromboembolism (VTE). The deficiency of natural anticoagulant (NA; protein C, protein S, or antithrombin) is relatively common in Asians and is conventionally screened by coagulation tests. The recent introduction of massive parallel sequencing (MPS) into clinical practice has revolutionized the diagnostic workup for GT.

Aims: This study aimed to characterize GT in Korean patients with VTE by using MPS.

Methods: The study subjects were the patients diagnosed with VTE who underwent MPS for GT between January 2019 and August 2021 at Samsung Medical Center, Seoul, Korea. Those with major risk factors, either transient or persistent, were excluded. Sixty-two thrombosis-related genes were sequenced on Illumina NextSeq 550Dx. Variants were interpreted according to the American College of Medical Genetics and Genomics/Association for Molecular Pathology and ClinGen Variant Curation Expert Panel and were finally classified as pathogenic/likely pathogenic variants (PV/LPV). variants of uncertain significance (VUS), or likely benign/benign variants. Only PV/LPV and VUS were included for analyses, and the patients with PV/LPV were considered as having GT.

Results: Total 121 variants (PV/LPV or VUS) were detected in 105 study patients. Among them, 28.9% (35/121) were PV/LPV, and 71.1% (86/121) were VUS. Fourteen variants (14/121, 11.6%) were novel, consisting of 5 PV/LPV and 9 VUS. Five novel PV/LPV were PROS1 Gly336Arg, SERPINC1 Cys127Phe, Gly199Metfs*86, FGG Phe220Serfs*5, and C4BPA Cys468*. As a result, 27 patients (25.7%) were assigned to have GT (25 with NA deficiency and 1 each with fibrinogen disorder and Factor V Hong Kong).

Conclusion(s): Our data of GT in VTE revealed the clinical utility of MPS. The majority of PV/LPV were observed in NA genes. VUS were more common than PV/LPV, and further studies involving larger, collaborative dataset are needed to elucidate the significance of VUS in GT.