scholarly journals Rare coding variation in paraoxonase-1 is associated with ischemic stroke in the NHLBI Exome Sequencing Project

2014 ◽  
Vol 55 (6) ◽  
pp. 1173-1178 ◽  
Author(s):  
Daniel Seung Kim ◽  
David R. Crosslin ◽  
Paul L. Auer ◽  
Stephanie M. Suzuki ◽  
Judit Marsillach ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Exome Sequencing ◽  
Paraoxonase 1 ◽  
Sequencing Project ◽  
Exome Sequencing Project

scholarly journals Imputation of coding variants in African Americans: better performance using data from the exome sequencing project

2013 ◽  
Vol 29 (21) ◽  
pp. 2744-2749 ◽  
Author(s):  
Qing Duan ◽  
Eric Yi Liu ◽  
Paul L. Auer ◽  
Guosheng Zhang ◽  
Ethan M. Lange ◽  
...  
Keyword(s):  
African Americans ◽  
Exome Sequencing ◽  
Sequencing Project ◽  
Exome Sequencing Project ◽  
Using Data ◽  
Coding Variants

scholarly journals Association Between Absolute Neutrophil Count and Variation atTCIRG1: The NHLBI Exome Sequencing Project

2016 ◽  
Vol 40 (6) ◽  
pp. 470-474 ◽  
Author(s):  
Elisabeth A. Rosenthal ◽  
Vahagn Makaryan ◽  
Amber A. Burt ◽  
David R. Crosslin ◽  
Daniel Seung Kim ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Absolute Neutrophil Count ◽  
Neutrophil Count ◽  
Sequencing Project ◽  
Exome Sequencing Project

scholarly journals AB0008 APPLYING WHOLE EXOME SEQUENCING TO FAMILIAL ANTIPHOSPHOLIPID SYNDROME: NEW PLAYERS IN A RARE DISEASE?

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1039.1-1039
Author(s):  
A. Barinotti ◽  
M. Radin ◽  
I. Cecchi ◽  
S. G. Foddai ◽  
E. Rubini ◽  
...  
Keyword(s):  
Immune Response ◽  
Ischemic Stroke ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Antiphospholipid Syndrome ◽  
Missense Mutations ◽  
Literature Research ◽  
Missense Variants ◽  
Vein Thrombosis ◽  
Whole Exome

Background:Antiphospholipid Syndrome (APS) is an autoimmune disease whose precise aetiology is still unknown, but the high heterogeneity of its manifestations and clinical course is presumably due to the occurrence of different mechanisms and alterations at different levels and pathways [1]. The first genetic studies in APS focused primarily on the human leukocytes antigen system region, but more recent data highlighted a role of other genes in APS susceptibility, primarily those involved in the immune response and in the haemostatic process.Objectives:We aimed to deepen the investigation of APS genetic background starting from a case of familial APS, analysing two siblings with thrombotic APS (Table 1), both triple positive for antiphospholipid antibodies (aPL).Table 1.Main clinical and laboratory characteristics of the patients included in the study.PatientAgeaPL ProfileRelevant Clinical History1 (F)51Triple positive (LA, aCL IgG, aβ2GPI IgG)Two episodes of ischemic stroke, one episode of CAPS (renal thrombotic microangiopathy, visual impairment, ischemic stroke)2 (M)47Triple positive (LA, aCL IgG, aβ2GPI IgG)Three episodes of deep vein thrombosis, regardless ongoing well conducted therapy vitamin k antagonist and additional retinal vein thrombosisLA: lupus anticoagulant; aCL: anti-cardiolipin antibodies; aβ2GPI: anti- β2 glycoprotein I antibodies; CAPS: catastrophic APS.Methods:Genomic DNA was extracted from peripheral blood and the samples underwent Whole Exome Sequencing (WES). Sequencing was done on a 100X coverage, and reads have been aligned to the human reference genome (GRCh37/hg19 assembly) using the Burrows–Wheeler Alignment tool (BWA). The mean sequencing depth on target regions was 170X for patient 1, 205X for patient 2, moreover, 99.50% of the targeted bases had at least 10X coverage for all the three donors. The resulting single nucleotide polymorphisms (SNPs) have been analysed through a step-by-step process based on their frequency population (using Genome Aggregation Database), their predicted effects on the protein (using VarSome) and a literature research about the genes carrying them. Moreover, genes previously associated with a pro-thrombotic tendency and with APS have been analysed in the two patients.Results:Starting from more than 120000 SNPs for each patients, the analysis led to reduce the list of SNPs of interest to 27 missense mutations. The complete literature research regarding the genes carrying these mutations allowed to further reduce the number of selected genes, focusing on those that exert a role potentially involved in APS pathogenesis and development. In particular, these genes (PLA2G6, HSPG2, BCL3, ZFAT, ATP2B2, CRTC3 and ADCY3) take part in the immune response and the vascular homeostasis. The list of the DNA missense variants of interest found in our cases of familial APS is resumed in Figure 2.Figure 2.List of DNA missense variants of interest found in patient 1 and 2. Genes potentially involved in APS pathogenesis and development are highlighted in bold.No mutations on genes known to be associated with a pro-thrombotic state (F5, F2, MTHFR, F13A1, PROC, PROS1, FGB and SERPINE1), or on genes previously associated with APS (B2GPI, PF4V1, SELP, TLR2, TLR4, GP Ia, GP1BA, F2R, F2RL1, TFPI, F3, VEGFA, FLT1, and TNF) have been found in the WES analysis.Conclusion:To some extent, this can be seen as a proof of concept of the complexity of APS. Efforts to interpret the genetic risk factors involved in the heterogeneous clinical features of the syndrome, for instance, the integration of WES and network-based approaches might help to identify and stratify patients at risk of developing APS.References:[1]Iuliano A, Galeazzi M, Sebastiani GD. Antiphospholipid syndrome’s genetic and epigenetic aspects. Autoimmun Rev. 2019;18(9).Disclosure of Interests:None declared

Sonographic evaluation of atherosclerosis burden in carotid arteries of ischemic stroke patients and its relation to paraoxonase 1 and 2, MTHFR and AT1R genetic variants

2017 ◽  
Vol 378 ◽  
pp. 146-151 ◽  
Author(s):  
Carmen Rosa Hernández-Socorro ◽  
Francisco Javier Rodríguez-Esparragón ◽  
Jennifer Celli ◽  
Juan Carlos López-Fernández
Keyword(s):  
Ischemic Stroke ◽  
Genetic Variants ◽  
Carotid Arteries ◽  
Paraoxonase 1 ◽  
Stroke Patients ◽  
Sonographic Evaluation

Analysis of paraoxonase 1 (PON1) genetic polymorphisms and activities as risk factors for ischemic stroke in Turkish population

2009 ◽  
Vol 27 (8) ◽  
pp. 558-567 ◽  
Author(s):  
Birsen Can Demirdöğen ◽  
Şeref Demirkaya ◽  
Aysun Türkanoğlu ◽  
Semai Bek ◽  
Emel Arınç ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Genetic Polymorphisms ◽  
Turkish Population ◽  
Paraoxonase 1
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