POS0780 MONOGENIC SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IN NORTHERN ISRAEL

Background Systemic Lupus erythematous (SLE) is a heterogenic clinical syndrome with a multifactorial etiology including diverse environmental, immunological and genetic causes and modifiers. Increasingly, utilizing next generation sequencing tooIs, monogenic forms of SLE have been identified. Objectives The aim of our study was to identify monogenic causes of SLE in the unique pediatric population of Northern Israel. Methods A retrospective and prospective study was carried out between 2010-2021 in a single tertiary pediatric medical center. Genetic testing including Whole exome sequencing (WES) was performed for select patients including family history of SLE, consanguinity and\or clinical findings suggestive of specific disorder. Results 75 children were diagnosed with SLE. 13/75 had one or more relatives with SLE, including a pedigree with 4 affected members. Mean age at presentation was 10.1±4.7. A monogenic disorder was identified in total of 7/75 of pedigrees. Four patients were diagnosed with Prolidase deficiency, one patient with ADAR1 mutation related to Aicardi–Goutières syndrome and one pedegree with APC5 mutations. Candidate variants in genes related to immune system were identified in one proband and her father requiring further study. Additional WES results are pending Conclusion We detected monogenic causes of SLE in a select cohort of patient in Northern Israel. Identification of a genetic basis for disease has direct clinical implication for patients and families and can also enhance our understanding of the pathogenesis and disease mechanisms involved in the more common sporadic forms of SLE. Disclosure of Interests ilia spivak: None declared, Tova Hershkovitz1 Grant/research support from: Regeneron Genetics center, Tarrytown, NY, USA, Rinat Zaid Grant/research support from: Regeneron Genetics center, Tarrytown, NY, USA, Karin Weiss Grant/research support from: Regeneron Genetics center, Tarrytown, NY, USA, Yonatan Butbul Aviel: None declared