A novel mutation in IL36RN underpins childhood pustular dermatosis. (16th February 2015) - Ellingford, J.M.
Abstract: Background: Chronic pustular dermatoses are severe and debilitating autoinflammatory conditions that can have a monogenic basis. Their clinical features are, however, complex with considerable overlap. Null and missense mutations in the genes encoding interleukin (IL)‐1 family (IL‐1 and IL‐36) anti‐inflammatory receptor antagonist (Ra) cytokines can underlie the development of severe pustular dermatoses. Objective: We present a clinical and genetic study of four children of Pakistani descent with similar clinical presentations and treatment course, each of whom suffers from a severe pustular dermatosis, initially described as a pustular variant of psoriasis. We use DNA sequencing to refine the diagnosis of two of the children studied. Methods: Bidirectional Sanger sequencing was performed on the coding regions of the IL‐1Ra and IL‐36Ra genes ( IL1RN and IL36RN, respectively), for the four affected children and their parents. Results: We identified a novel homozygous missense mutation in IL36RN in two siblings, and showed the molecular basis of the condition to be both distinct from psoriasis and distinct between the two families studied. Conclusions: We describe a novel mutation which underpins the diagnosis of childhood pustular dermatosis. Molecular diagnostics can be used to aid the clinical diagnosis and potential treatment of autoinflammatory conditions.