Ciliopathies: an expanding disease spectrum.

Pediatr Nephrol 2011 Jul 6;26(7):1039-56. Epub 2011 Jan 6.

Department of Nephro-Urology, Great Ormond Street Hospital, London, WC1N 3JH, UK.

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.

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http://dx.doi.org/10.1007/s00467-010-1731-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098370PMC
July 2011
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References

(Supplied by CrossRef)

SJ Ansley et al.
Nature 2003

JB Li et al.
Cell 2004

A Gherman et al.
Nat Genet 2006

PL Beales et al.
Nat Genet 2007

S Nonaka et al.
Cell 1998

P Satir et al.
Cell Motil Cytoskeleton 2007

D Woolley et al.
Essays Biochem 2000

EA Nigg et al.
Cell 2009

MV Nachury et al.
Cell 2007

LB Pedersen et al.
Curr Top Dev Biol 2008

DG Cole et al.
Cell 2009

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