Autoimmune phenotype with type i interferon signature in two brothers with ADA2 deficiency carrying a novel CECR1 mutation

Background: loss-of-function cecr1 mutations cause polyarteritis nodosa (pan) with childhood onset,an autoinflammatory disorder without significant signs of autoimmunity. herein we describe the unusual presentation of an autoimmune phenotype with constitutive type i interferon activation in siblings with adenosine deaminase 2 (ada2) deficiency. case presentation: we describe two siblings with early-onset recurrent strokes,arthritis,oral ulcers,discoid rash,peripheral vascular occlusive disease and high antinuclear antibody titers. assessment of interferon signatures in blood revealed constitutive type i interferon activation. aicardi-goutières syndrome (ags) was suspected,but no mutation in the known ags genes were detected. whole exome sequencing identified compound heterozygosity for a known and a novel mutation in the cecr1 gene. functional consequences of the mutations were demonstrated by marked reduction in ada2 catalytic activity. conclusions: our findings demonstrate that ada2 deficiency can cause an unusual autoimmune phenotype extending the phenotypic spectrum of pan. constitutive interferon i activation in patient blood suggests a possible role of type i interferon in disease pathogenesis which may have therapeutic implications. © 2017 the author(s).