Ciliopathies literature review examples


Cilia are ancient and evolutionarily conserved organelles which are found on cell surface. This organelle project from those cell surfaces to provide multifunctional biological roles in the organism. An important role that cilia has been known to perform for cells are the locomotion, sensation and reproduction. The implication of the defect in the cilia is that the cell that tend to depend on the organelles for proper performance will be limited in it role. There are many diseases that have been found to be associated with cilia defects. Since cilia occurred as important organelles of many cells, majority of the diseases or conditions found to be linked with the defect of cilia comes in form of syndromes.
The known defects involving cilia are ” primary ciliary dyskinesia, hydrocephalus, polycystic liver and kidney disease, and some forms of retinal degeneration” (Badano, Mitsuma, Beales & Katsanis, 2006). The new evidences relating to molecular and genetic studies have shown that ciliary defects can also result into a ” broader sets of development and adult phenotypes with problems involving mutation of the normal ciliary proteins which has been associated with nephronopthisis, Bardet-Biedl syndrome, Alstrom syndrome and Meckel-Gruber syndrome” (Badano, Mitsuma, Beales & Katsanis, 2006).
Understanding of the cilia defects at the molecular and genetic level have helped to highlight the broader scope of problems which made up ciliopathies in human. Can we then say the problems of ciliopathies are a genetic etiologic component with more of neurological affectation compared to other major systems in the body?


In the structural aspect of cilia, it is made up of large amount of proteins that help build the structure in form of complexes. The protein complexes tend to function in a coordinated manner to achieve the various forms locomotive, chemosensational or mechanosensational functions needed to be performed by the cells. These proteins are coded by certain genes and the implication of a mutation of a responsible gene is that there would be defect in the protein production hence problems with cilia functioning. The advancement in genetics has helped in detection of several forms of genes that when affected lead to a functional defect in the cilia causing a particular disorder.
A newly detected mutation affecting INPP5E gene by an international team of scientist has shown that gene to be linked with ciliopathies (Debra, 2009). The discovery is recent and shown the identified gene to be responsible for coding what is responsible for enzymatic conversion of a signalling molecules which is found to be associated with phosphatylinositol pathway (Debra, 2009). This pathway is an important pathway responsible for cilia functioning. The implication of this is that when there is a problem with what is needed to stimulate or contribute to the effectiveness of the pathway, the resultant effects is a problem with functioning of the cilia which is an important organelles that many cells depend on to achieve their major roles in their organs. Important diseases that defective pathway functioning has been found is that which relates to ” ciliopathies in mental retardation, retinal blindness, obesity, polycystic kidney disease, liver fibrosis, and ataxia” (Debra, 2009).
The case of a single gene ciliopathies is another strong support for the ‘all is about genetic for ciliopathies’ perceptions. A single gene defects will result in several major disorders or syndromes simply because of the location of cilia within the body which is widespread. The implication of that is that all organs where the cilia are present would be affected in cases of the mutation. Hildebrandt, Benzing, & Katsanis (2011) describe most of the single-gene ciliopathies and their clinical features in terms of their relationship with the cilium-centrosome complex. The cilium-centrosome aspect relates more to the aspect of issues with mitosis. This could be described in terms of formation of the cilium which most cells tend to engage in when there is a need for cilia related functions. Considering this complex makes it more of a structural defect although the genetic aspect is responsible for effective cell division.
It is also important to state that there are two major types of cilia: the primary type which is the commonest and the major focus of this literature review and the motile cilia which is responsible for locomotive aspect. Dyskinesia issues are produce from the motile cilia defect and it thus lead to important syndrome such as Kartagener’s syndrome. Evidences have shown that in both polycystic kidney disease and nephronopthisis, there is a genetic mutation of certain important proteins that are usually found to localize in the nonmotile cilia. The importance of those cilia proteins to various pathogenic roles in both polycystic kidney disease and other diseases plays an important role in supporting the need to classify some diseases as ciliopathies (Hildebrandt, Benzing, & Katsanis, 2011). The implication of this is that pleiotropic clinical effects found in those conditions provide additional evidence that the issue with ciliopathies is more of genetics than structural issues because of the problems with genes responsible for coding the important cilia proteins.
Lee & Gleeson (2011) have shown cilia to be more of pathologic significance in neurodevelopmental disorders. Their findings have shown that disparate syndromes are all due to primary cilia defects (Lee & Gleeson, 2011). The main issue as regards to that aspect is that which relates to the problem involving the key signalling pathways molecules. The author’s conclusion of the importance of cilia and understanding its associated neurological defects was based on their findings which show cilia to modulate several signal transductions. Those transductions were found to be important in cellular responses in neuronal functioning.
The advancement in technology which has helped in the discovery and understanding of signalling pathways have contributed greatly to the identification of the importance of such pathways in cilia. That has also helped linked cilia to some forms of developmental disorders and diseases. Ciliary functioning which helps in controlling extracellular fluid flow and outside-in-signalling all contribute to major cellular functions. The position of this organelle on the cell has been said to influence the actual function it will perform (Bisgrove & Yost, 2006). The implication of this roles and positioning is that when there is a problem with such, the actual factors responsible for cellular growth and functioning will be impaired. More than 30 proteins and their respective genes with mutations have been found and these were highlighted with the respective associated disease. Some are also found with but with unknown disease while some are associated with more than a single disease entity (Bisgrove & Yost, 2006). The roles of cilia in extracellular fluid flow and signalling control has led to the discovery of its contribution to most of the neurological disorders.
Primary cilium has now been proposed to be considered as an important etiologic factor in craniofacial disorders. This is because of the findings according to the researches by Zaghloul & Brugmann (2011). The conclusion according to contribution of cilia was due to the fact that most ciliopathies do have craniofacial abnormalities as a components and the second major reason being that, there is usually a problem with the signalling pathway and that is an important component of neurological functioning (Zaghloul & Brugmann, 2011). Signalling defects that are have been identified to be associated with ciliopathies are nonaconical Wnt signalling and planar cell polarity, Hedgehog signalling, and cell cycle control. Different genetic mutations results in the changes associated with the signalling defects (Hildebrandt, Benzing and Katsanis, 2011).
The family of proteins that have been found in relations to the Hedgehod signalling plays significant roles in the developmental context of humans especially the craniofacial development (Zaghloul & Brugmann, 2011). The Wnt signalling is related to various developmental processes which include ” cell proliferation, determination, differentiation and survival” (cited in Zaghloul & Brugmann, 2011). Most of the diagnosis of ciliopathies made now depends on the phenotypic expressions and classifications. The classifications that are being made for that phenotypic expression are the results of an increasing understanding of the genetic bases of ciliopathies.


There are several on-going researches as regards to ciliopathies. There are several aspects of those diseases that are yet to be uncovered. Advancing technology will surely help to provide tools to uncover those aspects that will provide an evidence based information. This is important in managing those conditions considering the impact of those conditions on the affected individual. The important findings in this literature review are that there are increasing evidences on the genetic aspects of ciliopathies. Most features of these groups of conditions are associated with neurologic components. The implication of that is the relationship of an important role of cilia in neuronal development and function. Most signalling pathways discovered to be associated with cilia functioning are related to neuronal functioning.


Badano, Mitsuma, Beales & Katsanis (2006). The ciliopathies: an emerging class of human genetic disorders. Pubmed.

Retrieved 13 December, 2011 from http://www. ncbi. nlm. nih. gov/pubmed/16722803
Bisgrove, B & Yost, J. (2006). The roles of cilia in developmental disorders and disease.
Review. Development 133, 4131-4143 (2006)
Debra, K. (2009). Mutations in gene linked to ciliopathies. Press Release.
Retrieved 14 December, 2011 from http://www. eurekalert. org/pub_releases/2009-08/uoc–mig080709. php
Hildebrandt, F., Benzing, T. and Katsanis, N. (2011). Ciliopathies. Mechanisms of disease.
Review article. The New England Journal of Medicine. 364: 16.
Lee, J. E. & Gleeson, J. G. (2011). Cilia in the nervous system: linking cilia function and neurodevelopmental disorders.
Current Opinion in Neurology. 2011, 24: 98-105.
Zaghloul, N & Brugmann, S. (2011). The emerging face of primary cilia. Review.
Genesis 49: 231-246 (2011).