[103]. Mutations involving multiple genes can be involved in individuals with Bardet–Biedl syndrome [104], and different mutations at the same locus of a single gene (CEP290) can result in three distinct disease syndromes (BBS, MKS, and NPHP) [1].
Finally, it is important to know that truncating mutations often cause severe developmental defects that result in prenatal and perinatal mortality, whereas hypomorphic mutations are more likely to cause organ specific diseases that are degenerative rather than developmental [105]. Since complete loss of ciliopathy‐associated genes often results in early lethality, it may be necessary to generate mice carrying hypomorphic alleles with a range of strengths in order to model ciliopathies [1]. The genetic mechanisms that underlie ciliary functions and thus determine ciliopathy phenotypes are extremely complex, with gene locus heterogeneity, allelic effects, and modifier genes all contributing to influence both the type and severity of disease, and pleiotropic phenotypes [106]. To further complicate matters, a growing number of ciliopathies can be classified as second order ciliopathies [15]. These include ciliopathies that are caused by mutations in genes encoding proteins not present in cilia, but that do influence cilia formation or functions. For example, there are motile ciliopathies resulting from mutations affecting specific nonciliary proteins involved in the cytosolic assembly of axonemal dynein complexes before they are imported into cilia [15].
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