Recurrent PROC and novel PROS1 mutations in Vietnamese patients diagnosed with idiopathic deep venous thrombosis

Abstract

Introduction Genetic mutations of PROC and PROS1 are well‐known risk factors for deep venous thrombosis (DVT) in the Asian population. However, the genetic profile of Vietnamese patients with DVT remains elusive. This study aimed to investigate the spectrum of genetic mutations of these two genes in Vietnamese patients diagnosed with idiopathic DVT. Materials and methods A total of 50 Vietnamese patients diagnosed with idiopathic DVT were recruited in this study. The entire coding regions of the protein C and protein S genes were amplified and directly sequenced to determine genetic alterations. Results Four and six genetic mutations were detected in protein C and protein S genes, respectively, in 24 Vietnamese DVT patients. PROC c.565C > T (p.R189W) was the most common mutation found in 13 out of 50 patients, while the mutations of PROS1 comprised three missense and three nonsense variants which diffuse along the gene. Conclusions This study shows that mutations of protein C and protein S genes are prevalent in Vietnamese patients diagnosed with idiopathic DVT, and PROC c.565C > T (p.R189W) was the most common genetic alteration.

Pathogenic Ala303Val mutation in the PROS1 gene is associated with the pathogenesis of Deep Vein Thrombosis

“…According to the analysis results of the in silico database software, the p.A303V mutation could be pathogenic especially since the pathogenic score was close to 1 and it was determined to be "effected", "probably damaging", and "disease causing". The p.Leu259Pro (p.L259P), p.Ser283Pro (p.S283P), p.Leu310Pro(p.L310P), p.Leu405Pro (p.L405P), p.Arg474Pro (p.R474P), p.Ala575Pro (p.A575P), p.Ala484Pro (p.A484P) mutations reported in previous studies were found to cause the disruption of the secondary structure (14,16). The p.A303V mutation detected in our study is in the early part of the LG1 domain.…”

“…Protein S (PS) deficiency is an independently-acquired inherited risk factor for DVT. The incidence of PS deficiency in venous thrombosis has been reported to be 2-15% (16)(17)(18). Studies have reported that genetic changes in PROS1 have a negative effect on the functionality of PS.…”

Comprehensive diagnostic approach and real-life treatment strategy in a Vietnamese pedigree with familial protein S deficiency

“…An interesting finding in this pedigree was the coexistence of PC deficiency and PROC heterozygous c.565C>T (p.Arg189Trp) mutation in patient III-2. This PROC mutation is also the most common mutation reported among Vietnamese patients with DVT with a low PC level 11 . The combined deficiency of PC and PS is rare, with a frequency of roughly 0.88% among patients with VTE, and is associated with an increased risk of thrombosis 15 .…”

Genotype–phenotype characteristics of Vietnamese patients diagnosed with Charcot–Marie–Tooth disease

“…Direct sequencing was used to confirm the identified pathogenic mutations in the probands and subsequently in first‐degree relatives using appropriately designed primers. The protocol for direct sequencing was described previously (Do et al., 2020 , 2021 ; Kiet et al., 2019 ).…”