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The recognition of the clinical overlap between discrete clinical entities attributable to ciliary dysfunction has led to the unification of such disorders under the ciliopathy module. Introduction Genetic and functional studies have recognized that defects in genes encoding components of the ciliary apparatus lead to an overlapping set of clinical phenotypes that include retinal degeneration, renal cystic disease, polydactyly and other skeletal abnormalities, fibrosis of various organs, and a complex range of anatomical and functional defects of the central and peripheral nervous system. Our data illustrate how genetic lesions can be both causally associated with diverse ciliopathies, as well as interact in trans with other disease-causing genes, and highlight how saturated resequencing followed by functional analysis of all variants informs the genetic architecture of disorders. 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