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

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