FRI0556 GENETIC SCREENING IN PATIENTS WITH UNDIFFERENTIATED PERIODIC FEVER SYNDROME
Authors: Ferhat Demir, Özlem Akgün Doğan, Yasemin Kendirci, Kubra Ermis Tekkus, Sezin Canbek, Nuray Aktay Ayaz, Levent Doğanay, Betül Sözeri
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Autoinflammatory diseases (AID) are a group of hereditary diseases characterised by inflammation periods accompanied with clinical findings such as fever, skin rash, lymphadenopathy, abdominal pain, musculoskeletal symptoms, and with sign of inflammation in the blood. Each disease has own typical clinical findings and they are associated with mutations in specific genes such as in MEFV gene in familial Mediterranean fever (FMF), MVK gene in hyperimmunglobulin D syndrome (HIDS), TNFRSF1A gene in tumor necrosis factor-alpha receptor associated periodic fever syndrome (TRAPS) and NLRP3 gene in cryopyrin associated periodic fever syndrome (CAPS) (1,2). Also in some patients with periodic fever syndrome (PFS), clinical signs of these diseases can be seen but no mutation can be detected in the related genes (3,4). There are also patients exhibit the incomplete phenotype of a disease or overlap signs of more than one AID. The diagnosis of these undifferentiated patients have difficult and may not be possible by a single target gene analysis (5). Screening of the periodic fever syndrome (PFS) panel including various AID genes may be beneficial to define the atypical cases. Molecular genetics has an important role for lead to diagnosis in these patients. <h3>Objectives</h3> The aim of this study was to investigate the genotypic diagnosis in patients with non-characteristic PFS findings for any AID. <h3>Methods</h3> This is a prospective study and conducted between June 2016 and December 2018. Next-generation sequencing (NGS) analysis was performed by using "Fever and AutoInflammatory Syndrome panel: Panel by Sophia Genetics" including 8 genes (MEFV, MVK, NLRP3, NLRP12, TNFRSF1A, TNFRSF11A, LPIN2 and PSTPIP1) in 30 patients with undifferentiated PFS. Clinical features and genetic results were evaluated together and final diagnoses were determined. <h3>Results</h3> Thirty patients included in the study did not have typical clinical features for any of the eight monogenic diseases in the PFS panel. In the result of the genetic screening; disease-causing mutation was found in MEFV gene in 12 patient, in NLRP3 gene in four patient, in NLRP12 gene in two patient and in MVK gene in one patient. Also, genetic variants of uncertain significance (VUS) in different genes were shown in five patient. No mutation was detected in remaining six patient. The final diagnosis was made by both phenotypic and genotypic data. 12 patients were diagnosed with FMF, four were FCAS, two were FCAS2, one was TRAPS and one was HIDS. Patients with negative genetic screening or had mutation as VUS, were followed as <b>undifferentiated</b> PFS. <h3>Conclusion</h3> Autoinflammatory diseases may not always be appear with typical clinical findings of related disease. In such patients, target gene sequencing and detection of underlying disease can be challenging. Our study has shown that the NGS analysis may help to determined the diagnosis in patients with non-characteristic PFS findings for any AID. <h3>References</h3> [1] Federici S, et al, An International Delphi Survey for the Definition of New Classification Criteria for Familial Mediterranean Fever, Mevalonate Kinase Deficiency, TNF Receptor-associated Periodic Fever Syndromes, and Cryopyrin-associated Periodic Syndrome. J Rheumatol. 2018Nov1. <h3>Disclosure of Interests</h3> None declared