Ciliopathies: an expanding disease spectrum

Abstract

Ciliopathies comprise a group of disorders associated with genetic mutations encoding defective proteins, which result in either abnormal formation or function of cilia. As cilia are a component of almost all vertebrate cells, cilia dysfunction can manifest as a constellation of features that include characteristically, retinal degeneration, renal disease and cerebral anomalies. Additional manifestations include congenital fibrocystic diseases of the liver, diabetes, obesity and skeletal dysplasias. Ciliopathic features have been associated with mutations in over 40 genes to date. However, with over 1,000 polypeptides currently identified within the ciliary proteome, several other disorders associated with this constellation of clinical features will likely be ascribed to mutations in other ciliary genes. The mechanisms underlying many of the disease phenotypes associated with ciliary dysfunction have yet to be fully elucidated. Several elegant studies have crucially demonstrated the dynamic ciliary localisation of components of the Hedgehog and Wnt signalling pathways during signal transduction. Given the critical role of the cilium in transducing “outside-in” signals, it is not surprising therefore, that the disease phenotypes consequent to ciliary dysfunction are a manifestation of aberrant signal transduction. Further investigation is now needed to explore the developmental and physiological roles of aberrant signal transduction in the manifestation of ciliopathy phenotypes. Utilisation of conditional and inducible murine models to delete or overexpress individual ciliary genes in a spatiotemporal and organ/cell-specific manner should help clarify some of the functional roles of ciliary proteins in the manifestation of phenotypic features.Electronic supplementary materialThe online version of this article (doi:10.1007/s00467-010-1731-7) contains supplementary material, which is available to authorised users.

Bardet–Biedl syndrome

“…Defective motile cilia can result in primary ciliary dyskinesias manifesting with bronchiectasis, infertility and left-right asymmetry. 43 Immotile (primary) cilia are thought to function mainly as a sensory organelle regulating the signal transduction pathways and have a '9 þ 0' configuration, similar in structure to the motile cilia but without the central pair. 12,14,44 Defects in immotile cilia are characterised clinically by retinitis pigmentosa, polydactyly, situs inversus, learning difficulties and cystic kidneys, liver and pancreas.…”

“…Ciliogenesis and maintenance is orchestrated via the basal body acting in concert with the BBSome, which in turn is modulated by a chaperonin complex and members of the Rab family of proteins. 43 Together these proteins facilitate intraflagellar transport (IFT). This cellular process of bidirectional movement of particles facilitates the formation and maintenance of the cilium (Figure 2).…”

Present Status and Advances in Autosomal Dominant Polycystic Kidney Disease

“…Defects in primary cilia are thought to play an important role in polycystic kidney disease [46,47]. According to the current hypothesis, primary cilium is a kind of sensory organelle.…”

Циліопатії, роль Wnt-сигнального шляху в перебігу гострого (постінфекційного) гломерулонефриту: огляд літератури та власне спостереження

“…Циліопатії спри-чинені мутаціями генів, які кодують білки війок, призводять до порушення їх функції [4]. У нирках…”