A Novel Nlrp3 Variant In Two Unrelated Patients With Cryopyrin-Associated Periodic Syndrome

Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory syndrome characterised by recurrent episodes of urticarial rash and fever. Diagnosis is based on characteristic clinical features and identification of disease-causing variants of the NLRP3 gene. However, there are several variants of the NLRP3 gene that have unknown significance. Here, we describe two unrelated Japanese patients with periodic fever and urticarial rash; clinical symptoms suggested Muckle-Wells syndrome. In both cases, genetic analysis revealed a novel heterozygous p.Met659Arg variant in exon 3 of the NLRP3 gene. Functional analyses confirmed this variant as the cause of the disease. Both patients were treated with canakinumab and their disease activity is well-controlled.