NOD2 and Cowden disease: The loss-of-function mutations in the caspase activation and recruitment domain 15 (CARD15) gene encoding nucleotide-binding oligomerization domain 2 (NOD2) and in the autophagy related 16 like 1 (ATG16L1) gene are the strongest genetic risk factors for CD (Inohara et al., 2005; Cho, 2008; Chen et al., 2009; Strober and Watanabe, 2011; Jostins et al., 2012; Philpott et al., 2014).