ITPR1 and aniridia-cerebellar ataxia-intellectual disability syndrome: This protein-structure-based analysis is likely to have wide applicability in the interpretation of mutations, particularly in the important “channelopathy” class of human disease genes.45, 46, 47 The iris hypoplasia, which typifies Gillespie syndrome, might be a consequence of lower level of residual function in ITPR1 (compared to SCA29) but, given that only specific residues are altered, it seems more likely that these mutations disrupt functional interactions that are critical to the formation and/or maintenance of the sphincter pupillae muscle.