Gain-of-function RAC2 variants presenting as autoinflammatory phenotypes

Abstract

Abstract Background An expanded spectrum of gain-of-function (GOF) mutations in Ras-related C3 botulinum toxin substrate 2 (RAC2) causes severe combined immunodeficiency (SCID) or combined immunodeficiency (CID), which present with various phenotypes; these immunodeficiencies are characterized by severe lymphopenia, recurrent sinopulmonary infections, bronchiectasis, invasive viral infections, or severe bone marrow hypoplasia. Autoinflammatory features are rarely reported. Method We describe the cases of two girls presenting with novel autoinflammatory phenotypes associated with GOF RAC2 variants. An up-to-date review of the literature was conducted to explore the various spectra of clinical manifestations in patients with GOF RAC2 variants. Results One patient presented with vasculitis and leg ulcers, whereas the other presented with juvenile idiopathic arthritis and severe uveitis. Conclusion Our data extend the spectrum of the clinical presentation of GOF RAC2 variants, which may be associated with autoinflammation, highlighting novel and unusual clinical phenotypes.