Somatic mosaicism of CIAS1/NLRP3 gene in two patients with chronic infantile neurologic, cutaneous, articular syndrome

Abstract

CINCA syndrome (chronic, infantile, neurological , cutaneous, articular syndrome) also known as neonatal-onset multisystem inflammatory disease (NOMID) represents the most severe form of cryopyrin-associated periodic syndrome ( CAPS). This condition was found to be associated with missense mutations in the CIAS1/NALP3/PYPAF gene, which encodes cryopyrin. Cryopyrin is a member of the cytoplasmatic protein family CATERPILLER, which is involved in inflammasome molecular platform assembly, leading to inflammatory immune response and apoptosis regulation. It has been hypothesized that mutant cryopirin spontaneously oligomerizes and induces the inflammasome activation with elevated IL-1β production and autoinflammatory phenotype. Causative CIAS1 mutations have been detected in only half of the patients with CINCA and the genetic cause of the disease in patients who tested negative remains unclear.