In these studies, three members of a kindred (the proband, his mother and his aunt), each with Crohn's disease of varying severity, were found to have a mutation in the T60 isoform of CARD8 that exhibited defective inhibition of the NLRP3 inflammasome; consequently, circulating patient monocytes exhibited increased IL-1β and IL-18 secretion upon NLRP3 inflammasome stimulation and the proband had increased serum IL-1β levels. Here, CARD8 is linked to Crohn disease.