Ciliopathies: an expanding disease spectrum

Pediatr Nephrol. 2011 Jul;26(7):1039-56. doi: 10.1007/s00467-010-1731-7. Epub 2011 Jan 6.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cilia* / metabolism
  • Cilia* / pathology
  • Ciliary Motility Disorders* / genetics
  • Ciliary Motility Disorders* / metabolism
  • Ciliary Motility Disorders* / pathology
  • Genetic Predisposition to Disease
  • Humans
  • Kidney Diseases* / genetics
  • Kidney Diseases* / metabolism
  • Kidney Diseases* / pathology
  • Liver Diseases* / genetics
  • Liver Diseases* / metabolism
  • Liver Diseases* / pathology
  • Mutation
  • Phenotype
  • Retinal Diseases* / genetics
  • Retinal Diseases* / metabolism
  • Retinal Diseases* / pathology
  • Signal Transduction / genetics