Ciliopathy

Although non-motile or primary cilia were first described in 1898, “cell biologists largely ignored them.” But “microscopists continued to document their presence in the cells of most vertebrate organisms.” The “primary cilium was long considered–with few exceptions–to be a largely useless evolutionary vestige, a vestigial organelle. Recent research has revealed an initial understanding that cilia are essential to many of the body’s organs”^[1].

Recent advances in mammalian genetic research have facilitated the elucidation of a molecular basis for a number of dysfunctional mechanisms in both motile and primary cilia structures of the cell. “Numerous critical developmental signaling pathways” essential to cellular development have been discovered. These are principally but not exclusively found in the non-motile or primary cilia. A number of common observable characteristics of mamallian genetic disorders and diseases are caused by ciliary dysgenesis and dysfunction. Once identified, these characteristics thus describe a set of hallmarks of a ciliopathy^[2].

Cilia have recently been implicated in a wide variety of human genetic diseases by “the discovery that numerous proteins involved in mammalian disease localize to the basal bodies and cilia.” For example, in just a single area of human disease physiology, cystic renal disease, cilia-related genes and proteins have been identified to have causal effect in polycystic kidney disease, nephronophthisis, Senior-Loken syndrome type 5, orofaciodigital syndrome type 1 and Bardet-Biedl syndrome^[3].

“Just as different genes can contribute to similar diseases, so the same genes and families of genes can play a part in a range of different diseases.” For example, in just two of the diseases caused by malfunctioning cilia, Meckel-Gruber syndrome and Bardet-Biedl syndrome, patients who carry mutations in genes associated with both diseases “have unique symptoms that are not seen in either condition alone.” The genes linked to the two different conditions “interact with each other during development.” Systems biologists are endeavoring to define functional modules containing multiple genes and then look at disorders whose phenotypes fit into such modules.

“The phenotypic parameters that define a ciliopathy may be used to both recognize the cellular basis of a number of genetic disorders and to facilitate the diagnosis and treatment of some diseases of unknown etiology“^[2].

• Alstrom syndrome^[2]
• Bardet-Biedl syndrome^[2],[3]
• early embryonic death (some cases)^[2]
• hydrocephalus (some cases)^[2]
• Joubert syndrome^[2]
• Meckel-Gruber syndrome^[2]
• nephronophthisis^[2],[3]
• orofaciodigital syndrome type 1^[3]
• polycystic kidney disease^[2],[3]
• polycystic liver disease^[2]
• primary ciliary dyskinesia^[2]
• retinal degeneration (some forms)^[2]
• Senior-Loken syndrome^[3]

• agenesis of the corpus callosum^[2]
• anencephaly^[2]
• breathing abnomalities^[2]
• cerebellar vermis hypoplasia^[2]
• Dandy-Walker malformation^[2]
• diabetes^[2]
• Ellis-van Creveld syndrome^[2]
• exencephaly^[2]
• eye movement abnormalities^[2]
• liver disease^[2]
• hypoplasia of the corpus callosum^[2]
• hypotonia^[2]
• reproductive sterility^[2]
• Jeune asphyxiating thoracic dystrophy^[2]
• Juvenile myoclonic epilepsy (JME) ^[4]
• Kartagener syndrome^[2]
• Marden-Walker syndrome^[2]
• “mental retardation/developmental delay” or “other cognitive defects“^[2]
• obesity^[2]
• polydactyly^[2]
• posterior encephalocele^[2]
• respiratory dysfunction^[2]
• “recurent respiratory infections“^[2]
• renal cystic disease^[2]
• retinitis pigmentosa^[2]
• sensorineural deafness^[2]
• situs inversus/Isomerism^[2]
• spina bifida^[2]

A wide variety of symptoms are potential clinical features of ciliopathy.

• Defective thermosensation or mechanosensation^[5].
• _{(add to the list, with citations, here)}

• The Ciliary Proteome Web Page at Johns Hopkins
• Katsanis Lab publications at Johns Hopkins Medical Center

Template:WikiDoc Sources