Functional consequences of a germline mutation in the leucine‐rich repeat domain of NLRP3 identified in an atypical autoinflammatory disorder

Abstract

This report is the first to describe a familial form of a cryopyrinopathy associated with a mutation outside of exon 3 of NLRP3. This finding, together with the known efficacy of anti-IL-1 treatments in these disorders, underlines the importance of screening all exons of NLRP3 in patients who present with atypical manifestations. In addition, the gain of function associated with this mutation in terms of activation of caspase 1 signaling was consistent with the observed inflammatory phenotype. Therefore, this study of the functional consequences of an LRR mutation sheds new light on the clinical relevance of in vitro assays.