In contrast to the concentrated distribution of mutations associated with BS or EOS, mutations associated with CD (a total of 31 mutations) were scattered throughout the NOD2 structure in all domains except HD1; 13 mutations mapped to the NBD, one to the WHD, seven to HD2 and ten to the LRR domain (Supplementary Table 1, Fig. 5c). This evidence concerns the gene NOD2 and Cowden disease.