Targeted next-generation sequencing reveals novel and known variants of thrombophilia associated genes in Saudi patients with venous thromboembolism

Athar, Mohammad; Ghita, Ibrahim; Albagenny, Amani A; Abduljaleel, Zainularifeen; Shadab, G. G. H. A.; Elsendiony, Ahmed; Halawani, Saeed H.; Alkazmi, Mohammad M; Alquthami, Khalid; Alkhuzae, Mohammad M; Althebyani, Abdulaziz A.; Bogari, Neda M.; Dannoun, Anas; Al‐Allaf, Faisal A.

doi:10.1016/j.cca.2021.05.012

Cited by 6 publications

(2 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SERPIND1 (heparin cofactor II) is a serine protease inhibitor that selectively inactivates thrombin without affecting other proteases involved in the blood coagulation cascade. A previous study indicated an association between mutations in the SERPIND1 gene and venous thromboembolism [ 34 ], yet there is currently no study about SERPIND1 gene and CVT. Evidences had indicated interactions between the hemostatic system and innate immunity, and the coagulation and complement cascades.…”

Section: Discussionmentioning

confidence: 99%

The genetic risk factors for cerebral venous thrombosis: a case-control study in a Chinese national comprehensive hospital

Wang,

Yao,

Yang

et al. 2024

Thrombosis J

View full text Add to dashboard Cite

Background About 13–25% of cerebral venous thrombosis (CVT) cases lack clear etiology, which may be associated with underlying genetic factors. This study aims to investigate genetic factors in CVT patients using whole exome sequencing (WES). Methods Thirty-eight CVT patients hospitalized underwent WES. 977 subjects with WES data from a community cohort study --the Shunyi cohort were as the control group. Using bioinformatics analysis, differential genes with rare damaging variants between two groups were filtered (P < 0.05). KEGG enrichment analysis was performed on the screened genes to identify pathways associated with CVT. Results Through analysis of medical history, routine tests, and imaging examinations, the etiology of 38 patients: 8 cases of antiphospholipid syndrome, 6 cases with hematologic diseases, 3 cases of protein C deficiency, and 2 cases of protein S deficiency. Five cases occurred during pregnancy or puerperium, and 3 cases had a history of oral contraceptive use, and so on. The etiology was unknown in 12 cases (31.6%), and the etiology of 4 patients were further clarified through WES: F9 c.838 + 1_838 + 16del, Hemizygote: F9 EX1-EX7 Dup; CBS c.430G > A, CBS c.949 A > G; F2 c.1787G > A; SERPINC1 c.409-11G > T. Comparing the WES data of two groups, a total of 179 different genes with rare damaging variants were screened (P < 0.05), with 5 genes of interest (JAK2, C3, PROC, PROZ, SERPIND1). Enrichment analysis of the 179 different genes revealed the complement and coagulation pathway and the mitogen activated protein kinases (MAPK) pathway were associated with CVT. Conclusion For CVT patients with unknown etiology, WES could help identify the cause of CVT early, which is of great significance for treatment decisions and prognosis. In addition to the complement and coagulation pathway, MAPK pathway is associated with CVT, potentially related to platelet regulation and inflammatory response.

show abstract

Section: Discussionmentioning

confidence: 99%

The genetic risk factors for cerebral venous thrombosis: a case-control study in a Chinese national comprehensive hospital

Wang,

Yao,

Yang

et al. 2024

Thrombosis J

View full text Add to dashboard Cite

show abstract

“…The NGS data analysis was completed in accordance with Athar et al [31]. In brief, amplicon sequences of the target region of our constructed Ion AmpliSeq panel genes were matched to the human reference genome hg19 (GRCh37) using Torrent Suite software after subsequent DNA sequencing on Ion PGM (version 5.12.0; Thermo Fisher Scientific).…”

Section: Analysis Of Ngs Datamentioning

confidence: 99%

Novel LDLR Variant in Familial Hypercholesterolemia: NGS-Based Identification, In Silico Characterization, and Pharmacogenetic Insights

Athar

Toonsi

Abduljaleel

et al. 2023

Life

Self Cite

View full text Add to dashboard Cite

Background: Familial Hypercholesterolemia (FH) is a hereditary condition that causes a rise in blood cholesterol throughout a person’s life. FH can result in myocardial infarction and even sudden death if not treated. FH is thought to be caused mainly by variants in the gene for the low-density lipoprotein receptor (LDLR). This study aimed to investigate the genetic variants in FH patients, verify their pathogenicity, and comprehend the relationships between genotype and phenotype. Also, review studies assessed the relationship between the LDLR null variants and the reaction to lipid-lowering therapy. Methods: The study utilised high-throughput next-generation sequencing for genetic screening of FH-associated genes and capillary sequencing for cascade screening. Furthermore, bioinformatic analysis was employed to describe the pathogenic effects of the revealed novel variant on the structural features of the corresponding RNA molecule. Results: We studied the clinical signs of hypercholesterolemia in a Saudi family with three generations of FH. We discovered a novel frameshift variant (c.666_670dup, p.(Asp224Alafs*43) in the LDLR and a known single nucleotide variant (c.9835A > G, p.(Ser3279Gly) in the APOB gene. It is thought that the LDLR variant causes a protein to be prematurely truncated, likely through nonsense-mediated protein decay. The LDLR variant is strongly predicted to be pathogenic in accordance with ACMG guidelines and co-segregated with the FH clinical characteristics of the family. This LDLR variant exhibited severe clinical FH phenotypes and was restricted to the LDLR protein’s ligand-binding domain. According to computational functional characterization, this LDLR variant was predicted to change the free energy dynamics of the RNA molecule, thereby affecting its stability. This frameshift variant is thought to eliminate important functional domains in LDLR that are required for receptor recycling and LDL particle binding. We provide insight into how FH patients with a null variant in the LDLR gene respond to lipid-lowering therapy. Conclusions: The findings expand the range of FH variants and assist coronary artery disease preventive efforts by improving diagnosis, understanding the genotype-phenotype relationship, prognosis, and personalised therapy for patients with FH.

show abstract

Molecular Testing for Factor V Leiden and Prothrombin Gene Mutations

Dillard,

DeSimone,

Rennert

2025

Transfusion Medicine and Hemostasis

View full text Add to dashboard Cite

Targeted next-generation sequencing reveals novel and known variants of thrombophilia associated genes in Saudi patients with venous thromboembolism

Cited by 6 publications

References 39 publications

The genetic risk factors for cerebral venous thrombosis: a case-control study in a Chinese national comprehensive hospital

The genetic risk factors for cerebral venous thrombosis: a case-control study in a Chinese national comprehensive hospital

Novel LDLR Variant in Familial Hypercholesterolemia: NGS-Based Identification, In Silico Characterization, and Pharmacogenetic Insights

Molecular Testing for Factor V Leiden and Prothrombin Gene Mutations

Contact Info

Product

Resources

About