Print Email Download Reference This Send to Kindle Reddit This
submit to reddit

The Differences Between Cilia And Flagella Biology Essay

Differentiated by the different movement patterns, the Cilia and Flagella both possess similar structures and compositions. In most of the cases cilia originate from the eukaryotic cell surfaces with a few exceptions of fungi and cells of higher plants. The presence of cilia in vertebrates is almost ubiquitous. However they are limited to have sensory functions in invertebrates (P. T. W.; 1995). The fluids over the epithelial surfaces are usually in motion by the beating action of cilia. Cilia are also responsible for the motility of the sperms of vertebrates and Chlamydomonas. The sensory cilia are responsive to light, odour, osmolarity, chemicals and sound. They also perform beating action for the motility or fluid movement. Cilia has a primary role to play in the signal transduction pathways as shown by the current studies, which control the intracellular Ca2+ levels including the Hedgehog (Hh) and the planar cell polarity (PCP) pathways (G,H,2008). Ciliary functions that are compromised can have deep consequences on the cellular homeostasis, are also indicated in the research studies involving the cilia/basal body/centrosome proteins with human genetic disorders. Phenotypes are formed by the ciliary proteins dysfunction, ranging from being organ specific (for instance the polycystic kidney diseases) to being broadly pleiotropic (for instance the Bardet-Biedl syndrome). A set of phenotypic indicators related to the ciliary dysfunction is developed from the complex disease spectrum and developmental mutant phenotypes. These also include the disparate phenotypes such as the kidney’s, livers and the pancreas cystic diseases. In addition these diseases also include the neural tube defects, postaxial polydactyly, situs inversus and the retinal degeneration. Research is underway to clarify the system of the affected genes and the molecular and cellular basis of these phenotypes (Brent W. Bisgrove and H. Joseph Yost).

Cilia structure and function:

Extending from the cell surface, the specialized plasma membrane covers the microtubule based axoneme that constitutes the cilium. Nine peripheral microtubule doublets makes up the axoneme, which are arranged around the central core that might have the possibility of containing either the 9+2 central microtubule and the microtubule 9+0 axoneme. The 9+2 cilia are motile and have dynein arms connecting the microtubule doublets. The 9+0 cilia are non-motile and don’t have the dynein arms. The dynein motor activity helps in the ciliary motility as it moves the microtubule doublets in a sliding motion relative to one another. The extension of the ciliary axoneme is observed from the 9 triplet microtubules of the basal body, a microtubule organizing centre (MTOC) which originates from the older pairs of the centrioles. The y-shape fibres indicated the transition zone that lies at the junction of the basal body and the ciliary axoneme. These y-shapes fibres extend from the outer doublets of the microtubule. The transition zone can function as a filter for the cilium which is acts in collaboration with the basal body’s internal structure. The transition zone regulates the molecules that go in and out of the cilium. The distal tips which connect the ends of the axonemal microtubules to the ciliary membrane are micro tubule capping structures that are complex in their function and its structure (Brent W. Bisgrove and H. Joseph Yost, (2006), the roles of cilia in developmental disorders and disease: 10.1242/dev.02595.).

Type of cilia:

The motile 9+2 cilia in mammals function in an orchestrated wavelike fashion, and are generally found to concentrate on the cell surface in large numbers. These are also part of the fluid and cell movements. The primary cilia as compared to the motile cilia are found as single immotile organelles from the cell surface. Found on majority of the mammal cell types, the primary cilia are highly adapted to perform the functions of specialized sensory cells. For instance the vertebrate retina has the photoreceptor proteins that are situated in a highly elaborated 9+0 cilium, which is connected to the cell body another connecting cilium originating from the basal body. Examples of 9+2 sensory cilia and 9+0 motile cilia in spite of the broad classification of the cilia into 9+2 motile cilia and 9+0 immotile sensory cilia are found. For instance the odorant receptors of the specialized olfactory neurons have been identified on the immotile 9+2 sensory cilia while the 9+0 motile cilia possessing dynein arms connected with the outer microtubule doublets and rotate were identified on the mouse embryonic node cells (Brent W. Bisgrove and H. Joseph Yost (2006)).

What is ciliopathy:

Ciliopathies resulting in the abnormal function or formation of the cilia comprise of a group of disorders which relevant to the genetic mutations encoding defective proteins. Cilia dysfunction can reveal itself as a constellation of features which include characteristics like, retinal degeneration, renal disease and cerebral anomalies owing to the fact that almost all vertebrate cells, cilia dysfunction have cilia as an element (R.H., L., (2010)).  In addition the cilia dysfunction can manifest itself as congenital fibrocystic diseases of the liver, diabetes, obesity and skeletal dysplasia’s. In about 40 genes the ciliopathic features have been associated to mutations. Various other disorders related to the clinical features constellations will be attributed to mutations in other ciliary genes with the identification of 1,000 polypeptides presently recognized within the ciliary proteome. Still more research is required to explanation the mechanisms behind the diseases phenotypes linked with the ciliary dysfunction. The components of the Hedgehog and Wnt signalling pathways during signal transduction have been explored in various researches to demonstrate the dynamic ciliary localisation. It was not unexpected considering the primary role of the cilium in the transduction of the outside-in signals that the aberrant signal transduction is expressed in the disease phenotypes which are part of the ciliary dysfunction. The developmental and physiological roles associated with the aberrant signal transduction in the expression of the ciliopathy phenotypes are being further explored and for this research is further required (J., T., 2010).


A short paper which was published in 1976 (B A Afzelius (1998)) reported the existence of a genetic disease which was caused by the immotile cilia. About 1 person in 3000 had these genetic diseases. The conclusion was based on the following facts which were:

Two papers in 1975 explained the ultra structure of the sperm tail obtained from 3 infertile men. These men had immotile but normal spermatozoa (V., H., (2002)). These had the absence of so called dynein arms which are responsible for the movement generation of cilia or sperm tails. No organism before had the absence of dynein arms, in spite the fact that the flagellar mutants of other types had been explained belonging to a unicellular green algae. One of these papers explained that the spermatozoa obtained from two brothers had the same genetic disorder in which the dynein proteins synthesis and the dynein arms assembly are defective.

It was assumed that those in the cilia would also be affected owing to the genetic defect involving the dynein arms in the sperm tail. Therefore observations on the tract of the two brothers were also done. The radioactively tagged aerosol inhaled was measured for a period of 2 hours. The muccolinary transport was either very slow are was almost absent in the system. Therefore it was deduced the dynein arms were defective or absent (B A Afzelius ,1998). Observations were then carried out on the bronchial cilia of a 4rth man with immotile spermatozoa, which showed the absence of dynein arms muccolinary transport in the tracheobronchial of the cilia and the spermatozoa. Situs inversus was found in the sperm ultra structure in 2 out of 3 men examined. The 3rd was one of the 2 brothers examined. All three men were observed to have chronic sinusitis and bronchiectasis. These two signs when combined with situs inversus are the three cardinal signs of Kartagener’s triad or Kartagener syndrome. The conclusion derived was that the aetiology of the disease is the cilia’s genetic defect. Chance will determine whether the normal or the reversed position will be assumed by the viscera during the embryogenesis while the normal dynein are absent.

Similar cases with the situs inversus absent or present in the immotile cilia syndrome will be demonstrated. Therefore the sub group of the immotile cilia syndrome would be the Kartagener syndrome. The chronic cough and expectoration of mucoid, mucopurulent sputum, bronchiectasis, chronic rhinitis and nasal polyposis, recurrent maxillary rhinitis, agenesis of the frontal sinuses, atelectasis, and often otitis before puberty are the results (V., H., 2002). Chronic rhinitis, sinusitis and bronchitis are the clinical expressions found from the early childhood. Treatments according the symptoms are given often considering the complications in the respiratory tract. Hence an early physiotherapy is required. About 1 in 68000 has the Kartagener syndrome and the instance of occurrence of the immotile cilia syndrome was found to be 1 in 34000. About 1 in 8000 person of the situs inversus was found in Scandinavia and 1 in 11000 in the USA. Bronchiectasis was found in the situs inversus patients with a rough estimate of 4rth or 5th of all the people to have this. This means that about 1 in 25000 have the Kartagener syndrome of cilia syndrome. Research conducted on families showed that Kartagener syndrome or an incomplete syndrome was found to be present in 30 subjects thus showing an absence of situs inversus. The results showed that the syndrome is inherited as an autosomal recessive mutant (B A Afzelius (1998)).

Several diseases are associated with mutation of ciliopathies.

The genetic disorders, both genetic syndromes and genetic diseases, as showed by the recent research, not previously linked to the medical literature are being assumed as the primary factor behind the existence of a wide range of medical symptoms that appear in the disorders. Ciliopathies is the name give to this new emerging type of diseases. A dysfunctional molecular mechanism may be the cause in the primary cilia structures, organelles which may be found in various diversified cellular types in the human body. Various critical developmental signalling paths are affected by the cilia defects, which are primary to the cellular development and also provide an admirable hypothesis for the multi symptomatic nature of the diseases and syndromes. Primary ciliary dyskinesia, Bardet-Biedl syndrome, polycystic kidney and liver disease, 

Nephronophthisis, Alstrom syndrome, Meckel-Gruber syndrome and some forms of retinal degeneration are the types of ciliopathies known

Primary cilia dyskinesia PCD:

Inherited as an autosomal recessive, the Primary ciliary dyskinesia (PCD), is a rare condition but with the possibility of inheritance pattern. Its occurrence is underestimated with a late diagnosis which is usually detected during the cases of screening siblings of an index case. 70 cases will be found born per year in spite of the presence of about 1 in 15000 while the UK has 3000 cases. On the contrary about 90 cases have been recognized by the UK PCD support group. It is assumed that a presence of one tenth of the known cases but with the possibility that a large quantity of the undiagnosed patients are present (A. Bush, P. Cole, M. Hariri, I. Mackay, G. Phillips, C. O'Callaghan, R. Wilson, J.O. Warner (1998). As the diagnosis has possibilities for the upper and the lower respiratory tract diseases, therefore the matter is being given importance besides its academic value. Diseases for instance such as the prevention of bronchiectasis by aggressive use of physiotherapy and antibiotics, abstaining from the usage of inappropriate ear nose and throat (ENT) procedures and thoracic surgery, and assessment and treatment of deafness. The PCD’s diagnostic awareness has been targeted through this paper through the discussions involving the indications for the referral of the diagnostic testing and to underline the criteria for the diagnosis. The writer will present various specialities related to the clinical and research interests in PCD (G., H., (2008)).

Epidemiology and genetics of PCD/KS:

The estimates of PCD occurrence ranges from 1/15,000 to 1/60,000 live births while the rest of the estimates state the PCD occurrence to be 1/12,500. As the case of situs inversus is found to be more therefore KS occurrence comes out to range between 1/30,000 and 1/120,000 live births (or 1/25,000). Especially in the case of PCD patients with the usual visceral arrangement (CDO, ciliary dysfunction only), the disease frequency is underestimated (Maciej Geremek, Micha Witt (2004)). The diagnosis becomes more inconvenient owing to the mirror arrangement of the organs absent while the CDO patients are often diagnosed late. Autosomal recessive is the type of inheritance present. The functional defects of the cilia which are categorized as the dysmoyility or immotility are the main reason behind the PCD symptoms. The characterization of 18 varying ultra structural defects have been done which are outer dynein arm defects, inner dynein arm defects, microtubule transpositions, radial spokes defects, and the absence of nexin links (H.B., P., (2005)).

The electron microscopy has not been able to reveal ultra structural defects in about 10-20% of the patients, in spite of the fact that their cilia are immotile. The primary dysfunction of the ciliary apparatus has been able to cause PCD which is the first human disorder caused by it. Current studies have linked 2 other disorders pathomechanically to the epithelial cilia. The intraflagellar transport damage in the non-motile primary cilia of the kidney epithelial cells can lead to polycystic kidney disease (Maciej Geremek, Micha Witt ,2004). The primary cilia form the outer parts of the retinal photoreceptors. The connecting cilium which is a short fragment in a mature photoreceptor stays between the outer and the inner parts of the cones and the rods. The opsin is moved from the inner parts to the outer parts through connecting cilia, in the process which is same as the intraflagellar transport. The defect is assumed to be the primary reason behind RP.

The various defects that affect the ciliary structure and the function in the PCD have not been clearly explained on the basis of genetics. Around 250 types of the polypeptides have been recognized in the ciliary axoneme of the lower organisms. The human axoneme is expected to have similar amount of proteins. Mutations belonging to 250 various genes coding for the different ciliary proteins is less likely to create similar ciliary dysfunction’s pathologic results. If the case was true then the occurrence of PCD would also be higher than expected. Even in the case of the gene being heterozygous, there is possibility that many ciliary protein gene mutations may be life threatening. On the contrary come of the ciliary functions may not be affected by the gene mutations at all, owing to the redundancy of the comkon genetic functions like the dynein. The low occurrence of the KS and the PCD says that mutations in some of the genes may cause the diseases. The gene causing the PCD can be mapped out through the application of 2 strategies. The first is the candidate gene approach which consists of study involving the genes that have been selected on the basis of the purported ciliary function or animal/plant models of the disease. The next strategy involves the linkage study that constitutes of identifying the genomic markers associated with the PCD family’s diseases (W.Micha, G.Maciej (2004).

Diagnosing primary ciliary dyskinesia:

One of the defects among the various ciliary defects is the main reason behind the PCD which will lead to the ineffective muccolinary clearance. The diagnosis is mostly delayed in spite of the PCD patients having symptoms from birth or early infancy. There is also a possibility that most of the patients are not even diagnosed. The delay or the failure in the diagnosis will lead to bronchiectasis as a result of lung damage and the obstruction in the airways of the lungs with secretions thus increasing the infection. The lungs can be protected from damage in case of an early diagnosis by specialist respiratory care. Inadequate ear, nose and throat (ENT) surgery can be the result of a failure to diagnose the disease. The hearing loss will not be improved to the slightest even with the help of grommet insertion leading to oral discharge. Many PCD patients are found in the infertility clinics because of inaccurate diagnosis. Male infertility is not necessary but may be the case owing to the sperm tails being affected by the PCD as well as the ectopic pregnancy owing to the defective cilia movement in the fallopian tube (C., R., 2006).

There has been an absence of standardization with diagnosis being provided on an ad hoc basis with the patients having no access to the testing facilities in the UK. Although screening tests are available but they are still having issues. For instance in the case of the saccharin test , which is used to analyze the mucociliary function has inconvenience in applying it and is not reliable for children. The most sensitive and accurate test for the PCD is the measuring of the nasal nitric oxide which is the lowest in the PCD patients. But its drawback is its unavailability and it cannot be performed on children. The diagnostic testing has been improved owing to the developments in the new methods used. Many of the PCD patients are not recognized when using the traditional measuring system of the ciliary beat frequency as these patients may have a normal ciliary beat frequency but will have an abnormal beat pattern (Christopher O’Callaghan, Mark Chilvers, Claire Hogg, Andrew Bush, Jane Lucas (2007)).

Measurement of ciliary beat frequency, high speed analysis of ciliary beat pattern, detailed electron microscopy of ciliary ultra structure and cell culture from biopsies in cases of diagnostic uncertainties are now available for the diagnostic analysis. Although the genetic based technologies are developing, there is still time before the will be used widely for the diagnosis because of the multiple phenotypes of the diseases and the usage of more than 200 varying protein types used in the ciliary axoneme construction. The hospital consultants become a good sure for the referrals for the diagnostic services but the service does not provide care for the PCD patients. As there is no experiential data available for the care of the PCD patients, it is better to try out a model which is similar to the CF where the patients should be provided with specialist paediatric respiratory consultant or a thoracic physician with an interest in the CF or non-Cf bronchiectasis. A national data abase will be established for the PCD which will facilitate the clinical trials and help improve the management by providing evidence (Christopher O’Callaghan, Mark Chilvers, Claire Hogg, Andrew Bush, Jane Lucas (2007)).

Nephronophthisis (NPHP)

Nephronophthisis (NPHP), is also known as Familial juvenile Nephronophthisis (FJN). FJN is equally distributed in males and females and is an uncommon condition. The disease develops typically at the age of 20 years and according to some studies at the age of 13 years as it progresses to the end stage of the renal disease. The speedy progression to the renal failure, as in the genetic renal diseases such as the autosomal dominant polycystic kidney disease or hereditary nephritis, is determined by the type and the seriousness of the genetic defect (Niaudet.P ( 2001)). Renal interstitial fibrosis, interstitial cell infiltrates, and tubular atrophy with cyst development at the corticomedullary junction are the histologic findings in the NPHP characterized as such. The infantile NPHP is an exception while the rest of the NPHP variants have the same renal histological pattern. The infantile NPHP demonstrates an extra feature which is primary for the autosomal dominant or recessive polycystic kidney disease like the einstabce of kidney enlargement, absence of the tubular basement membrane with irregular properties of the NPHP. In addition the cyst present outside the meullary region NPHP is a genetically heterogenous disorder. The identification of 6 genes has been done through positional cloning such as: NPHP on chromosome 2q13 NPHP2 on 9q22, NPHP3 on 3q22, NPHP4 on 1p36, NPHP5 on 3q21.1, and NPHP6 on 12q21.3. Large homozygous elimination of the NPHP1 gene is demonstrated by 25-30% of the patients. The NPHP1 genes through 4 have seen to react with ulia Hoefele, Matthias T.F. Wolf, John F. O’Toole, Edgar A. Otto, Ulla Schultheiss, Georges De schenes, Massimo Attanasio, Boris Utsch, Corinne Antignac, and Friedhelm Hildebrandt (2007).

olecular and genetic basis of NPHP:

The NPHP is concerned with a growing number of genes which will be reviewed with respect to the phenotype, frequency and the most common diseases associated with it. Accompanied by a homozygous single gene mutations/deletion, the NPHP is mostly associated with autosomal recessive disease, also having compound heterogenous mutations occurring in the single NPHP gene. The accurate genetic counselling and molecular diagnosis is facilitated by it. Although the oligogenicity has been documented in which the allelic variants of the multiple loci are the contributing factors of the disease. The NPHP gene mutation, in an epistatic way , will modulate the phenotype. Thus the possibility of a wide range of the spectrum of the clinical variants with mutants is increased. The nephrocystins, or the encoded NPHP proteins have typical multiple domains (Roslyn J Simms, Lorraine Eley and John A Sayer (2009)).

NPHP1 and nephrocystin:

By using the positional cloning methods the NPHP1 was the first one to be identified as the NPHP gene in the consanguineous families. The most frequently observed genetic abnormality is the homozygous eliminations are of B250 kb DNA in the region 2q13. The compound heterozygosity for the NPHP1 gene eliminations combined with a single point mutation in the NPHP1 gene is an example of other mutations. About 25% of the NPHP cases are based on NPHP1. The congenital OMA type and Senior– Loken and also give rise to JSRD phenotypes may be linked with the NPHP1 mutations. The nephrocystin- 1, is the product encoded by the NPHP1. The localization of the Nephrocystin-1, is done to the primary renal cilium19 and to epithelia cell adheren junctions. The localization of the primary cilia has been recently refined to the transition zone in the renal and the respiratory epithelia and to the cilia connected with the photoreceptor cells. The casein kinase 2 phosphorylation and an interaction with PACS-1 determine the targeting of the nephrocystin-1 to the cilia’s transition zone. In addition the interaction of the Nephrocystin-1 with other nephrocystins is also found and indications are found of the function of the complex proteins in multiple intracellular locations which include the cilium, cell– cell adherens junctions and at focal adhesions. The renal collecting ducts are where the human kidney nephrocystin-1 is expressed (Roslyn J Simms, Lorraine Eley and John A Sayer(2009)).


INVS/NPHP2 and inversin:

The infantile NPHP are the result of mutations in the INVS/NPHP2. The NPHP cases caused to 1% by the mutations. The gene which has the dynamic distribution during the cell cycle 46 encodes the protein named inversin and is expressed in the renal cilia 19,46,47 INVS mutations causing situs inversus. The human disease is mimicked by the knockout animals with large at an early stage with huge cystic kidneys, situs inversus and the hepatobiliary.

The uncommon but noted link with the INVS mutations is the Malformations. Retinitis pigmentosa. In the Wnt signalling, the inversin plays an important role also performing the task of switching between the canonical and the non canonical Wnt signalling pathways 50,51 . Thus is also needed for the movement of the convergent extension. In the development of the nephron, the inversin plays a vital role in the developing nephron and the tubular architecture’s maintenance. The dividing and the reorganizing task with help of the coordinated ability of the epithelial cells to form and maintain tubular structures lies on the planar cell polarity (PCP) signalling. The proteins mediate the PCP signalling, which are linked with the primary cilia/basal body complex like the inversin 50. The pathopysiology of the cyst development is associated with its disruption (Roslyn J Simms, Lorraine Eley and John A Sayer(2009)).

.NPHP3 and nephrocystin-3:

Diversified phenotypes are produced by NPHP3 mutations. The large Venezuelan kindred who exhibits the NPHP, identifies the mutation. The hepatic fibrosis and the retinal degeneration are associated with the NPHP3 mutations in some affected individuals. The NPHP3 phenotype mutations will be expended to include Meckel– Gruber like syndrome. nephrocystin-3 is encoded by NPHP3 which is found to react with the nephrocystin-116 and inversin, which also inhibits canonical Wnt signalling. Pcy , a mouse model of the NPHP type 3, demonstrates the cystic kidney disease. This disease only reacts to the aquaretic agents/vasopressin-2-receptor antagonists NPHP4 and nephrocystin-4 (alias nephroretinin) treatment. The nephrocystin-4 (alias nephroretinin), is encoded by the NPHP4 which is a highly conserved protein that reacts with the nephrocystin- 1. Isolation of NPHP, NPHP with RP and NPHP with OMA. May be caused by 42 Nephrocytsin-4 complexes with a-tubulin and localized primary cilium and basal bodies NPHP4. According to recent reports the nephrocystin-4 reacts with RPGRIP1L.(Roslyn J Simms, Lorraine Eley and John A Sayer(2009))

NPHP5 and nephrocystin-5:

Nephrocystin-5 is encoded by the gene, NPHP5/IQCB1. There are two IQ calmudulin association or binding sites in this protein. It actually surrounds a domain which is coiled in shape. Nephrocyctin-5 binds with the calmodulin by associating with IQ binding sites, and then it co-locolizes with the cilia. The resultant is a RGPR complex with the protein. There has been severe retinal degeneration as phenotypic manifestation in most of the NPHP5 mutations. (Senior-Loken Syndrome) (Roslyn J Simms, Lorraine Eley and John A Sayer (2009)).

NPHP6/CEP290 and nephrocystin-6:

The nephrocystin-6 protein is encoded by the NPHP6 gene which is also called CEP290. There are several clinical diseases which are due to the mutations in the NPHP6 gene. These diseases or clinical phenotypes of said mutation include Senior-Loken Syndrome, JSRD, NPHP, MKS and BBS. About 221 % patients of LCA have also found to have mutation in NPHP6, which takes it to be the most common reason for genetic defect in isolated LCA. The rd16 is the mouse model for Nphp6/Cep290 disease and mimics the human disease state. It has early retinal degeneration, but it does not have any clinical condition related to the brain or kidneys. cAMP transcription factor which is called CREB2/ATF4, is activated by the interaction of Nephrocystin-6. The NPHP who have NPHP1 homozygous eliminations define the heterozygous mutations in the NPHP6 . The heterozygous NPHP4 missense mutation in an individual suffering from the Senior-Loken syndrome was explained by the heterozygous nonsense mutation in NPHP6. The tendency to the digenic and the oligogenicity was reported recently to other NPHP genes (Roslyn J Simms, Lorraine Eley and John A Sayer (2009)).


The encoding of the Kruppel-like zincfinger transcription factor GLIS2 which localizes the primary cilia and the nucleus, is done by the gene NPHP7/GLIS2. The affected members having isolated the NPHP by the Oji –Cree Canadian family, and the early onset renal failure since 8 years still remaining a rare genetic reason of the NPHP. Increased rates of the Apoptosis, was shown by the mouse model of the targeted Glis2 disruption, with the tubular atrophy and fibrosis (Roslyn J Simms, Lorraine Eley and John A Sayer (2009)).


The protein named as retinitis pigmentosa GTPase regulator interacting protein 1-like protein (RPGRIP1L) was encoded by the RPGRIPIL gene. The Fetuses which were affected by the MKS and patients with JSRD had mutations reported in them. Additional features like scoliosis, polydactyly, pituitary agenesis and partial growth hormone deficiency, reminiscent of RHYNS syndrome were revealed in some patients. The phenotype and genotype relationship can be drawn , relevant to the RDGRIPIL mutations, as homozygous truncating mutations which were the cause behind MKS while the JSRD is caused by the homozygous missense mutations. A centrosomal proteins called the RDGRIPIL, reacts with nephrocystin-4. A loss of interaction with is conferred with the nephrocystin-4 by the JSRD causing mutations in the RPGRIPIL. The inactivation of the mouse ortholog Rpgrip1l (Ftm) is represented by the mouse model Ftm_/_ (Fantom or fused-toe mouse) and the cerebral, renal and hepatic JSRD and the MKS defects are recapitulated (Roslyn J Simms, Lorraine Eley and John A Sayer (2009)).

NPHP9/NEK8 and NEK8:

The NEK8 protein is encoded by the NEK8 gene except in the mitosis a related kinase 8. Two families with the NPHP and one consanguineous family with

Infantile NPHP explains the mutations. A single heterozygous NEK8 mutation was observed in one family of the NPHP homozygous NPHP5 which is responsible for the diseases phenotype. The rare nature of the NEK8 mutations and the contributing NEK8 to the oligogenici in the NPHP patients was demonstrated by these results. The missense mutation (G448V) in Nek8 is found in the jck mouse model of cystic kidney disease. A protein complex is created by the combination of Nek8 and polycystin-2, which supports the argument that there are mechanisms commonly known forming the NPHP and ADPKD. (Roslyn J Simms, Lorraine Eley and John A Sayer ,2009).

Diagnostic methods and treatment:

Variable sized cysts are shown in the kidneys of FJN that are distributed in an irregular pattern at the corticomedullary junction and the medulla. Medullary cysts are often not found in the renal biopsies performed at an early stage, occur at the latter stage of the course. The light microscopy enables the sight of severe tubule damage (Niaudet.P (2004). The atropic tubule groups having a thick basement membrane, alternate with the dilated or collapsed tubules. The tubule basements undergoing changes show that the FJN is presented. The most prominent feature is the homogenous or the multilayered thickening of the basement membrane although the basement membrane disintegration can also be seen. The new inflammatory cells have a moderate interstitial fibrosis. Secondary segemental sclerosis is seldom found in advanced diseases although the glomeruli are often normal. The detection of the homozygous eliminations of about 250 kb on chromosome 2p12, by the absence of polymerase chain reaction amplified genomic DNA markers. 70% of the patients are quickly diagnosed which eliminated the need for renal biopsy (Niaudet.P (2001)).

The correction of the water and the electrolyte imbalance is the only therapy for FJN. Transplantation with dialysis is the preferable approach for the end stage renal disease. There is no occurrence of the tubule injury in the transplanted kidney which is void of any abnormality (Niaudet.P (2001)).

The PCR can conveniently screen the genetic tests followed by Adequate genetic counselling, homozygous or heterozygous NPHP1 elimination in 25% of the cases. Direct sequencing may be applied for other NPHP genes. In the presence of the molecular genetic diagnosis the necessity of the renal biopsy is eliminated. In case of the absence of a molecular diagnosis a renal biopsy would be the choice to confirm the presence or absence of NPHP (Roslyn J Simms, Lorraine Eley and John A Sayer (2008)).


The cilia’s role in the development of many tissue types such as the kidney,brain,liver,eyes and bone is indicated by the broad spectrum of phenotypes. Differing disorders are the result of mutant gene with the genetic heterogeneity as a common feature of the ciliopathies hence making the identification and the categorization more vague. BBS is thought to be associated with 12 genes which show that the common oath ways and complex are the constituting members of the products. The interactions with the similar pathways and complexes, are associated with the proteins involved in the ciliopathies. At the various cellular locations, the ciliary proteins are more inclined to be in complexes, where they mediate processes like the information of the intracellular junctions, cell to cell contact and the centrosome movements.

Print Email Download Reference This Send to Kindle Reddit This

Share This Essay

To share this essay on Reddit, Facebook, Twitter, or Google+ just click on the buttons below:

Request Removal

If you are the original writer of this essay and no longer wish to have the essay published on the UK Essays website then please click on the link below to request removal:

Request the removal of this essay.

More from UK Essays

Doing your resits? We can help!