Systemic lupus erythematosus (SLE) is a complex autoimmune disease marked by wide range of system dysfunctions. Traditionally we used to think that autoimmune disease arise as a result of failure of adaptive immune system to distinguish self and nonself antigens. Howerer, as in many inherited immunodeficiencies, frequently we see that inherited innate genetic mutation play pivotal part in autoimmune phenotype as well. DNASLE13 is endonuclease that is intimately involved in digestion of apoptotic micropatricles associated DNA and in prevention of anti-DNA antibody formation. When mutated, triggers SLE development. Aim was to describe patient with early-onset hypocomplementemic urticarial vasculitis who developed SLE at age 10,5y, with skin, lungs, heart, gastrointestinal, hematopoetic, serosal membranes, musculoskeletal and kindey involved , and positive ANA, anti-dsDNA, hypocomplementemia and lupus anticoagulant.
next-generation sequencing (NGS) was performed on TruSightOne sequencing kit (4813 genes) for all autoinflamatory diseases and interferonopaties. Results were confirmed by Sanger sequencing.
NGS of patient revealed homozygous mutation in exon 6 of DNASE1L3 gene (Deoxyribonuclease 1 Like 3) : one-nucleotid deletion NM_004944.3:c.643delT in egzon 6 of the, state. Mutation was described in HGMD base as disease causing mutation of SLE. In silico predictive analysis showed it as patological mutation (Mutation taster, CADD Phred 35, ACMG criteria). Mutation in DNASE1L3gene are SLE causing mutation (OMIM #614420).
we identified patient with DNASE1L3 mutation causing lupus erythematosus in patient with early-onset hypocomplementemic urticarial vasculitis syndrome pointing to dysregulation of nucleic acid sensing and degradation.