ciliary motility disorders


Summary: Conditions caused by abnormal CILIA movement in the body, usually causing KARTAGENER SYNDROME, chronic respiratory disorders, chronic SINUSITIS, and chronic OTITIS. Abnormal ciliary beating is likely due to defects in any of the 200 plus ciliary proteins, such as missing motor enzyme DYNEIN arms.

Top Publications

  1. Jorissen M, Bertrand B, Eloy P. Ciliary dyskinesia in the nose and paranasal sinuses. Acta Otorhinolaryngol Belg. 1997;51:353-66 pubmed
    ..However, these investigations are not always conclusive. Functional and ultrastructural ciliary evaluation after ciliogenesis in tissue culture is essential and crucial. ..
  2. Fliegauf M, Benzing T, Omran H. When cilia go bad: cilia defects and ciliopathies. Nat Rev Mol Cell Biol. 2007;8:880-93 pubmed
    ..Several molecular mechanisms involved in cilia-related disorders have been identified that affect the structure and function of distinct cilia types. ..
  3. Parisi M. Clinical and molecular features of Joubert syndrome and related disorders. Am J Med Genet C Semin Med Genet. 2009;151C:326-40 pubmed publisher
  4. Walczak Sztulpa J, EGGENSCHWILER J, Osborn D, Brown D, Emma F, Klingenberg C, et al. Cranioectodermal Dysplasia, Sensenbrenner syndrome, is a ciliopathy caused by mutations in the IFT122 gene. Am J Hum Genet. 2010;86:949-56 pubmed publisher
    ..Still, by identifying CED as a ciliary disorder, our study suggests that the causative mutations in the unresolved cases most likely affect primary cilia function too. ..
  5. Kobayashi Y, Watanabe M, Okada Y, Sawa H, Takai H, Nakanishi M, et al. Hydrocephalus, situs inversus, chronic sinusitis, and male infertility in DNA polymerase lambda-deficient mice: possible implication for the pathogenesis of immotile cilia syndrome. Mol Cell Biol. 2002;22:2769-76 pubmed
    ..Collectively, Pol lambda(-/-) mice may provide a useful model for clarifying the pathogenesis of immotile cilia syndrome. ..
  6. Garcia Gonzalo F, Corbit K, Sirerol Piquer M, Ramaswami G, Otto E, Noriega T, et al. A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition. Nat Genet. 2011;43:776-84 pubmed publisher
    ..Thus, a transition zone complex of Meckel and Joubert syndrome proteins regulates ciliary assembly and trafficking, suggesting that transition zone dysfunction is the cause of these ciliopathies. ..
  7. Sharma N, Berbari N, Yoder B. Ciliary dysfunction in developmental abnormalities and diseases. Curr Top Dev Biol. 2008;85:371-427 pubmed publisher
  8. Omran H, Haffner K, Volkel A, Kuehr J, Ketelsen U, Ross U, et al. Homozygosity mapping of a gene locus for primary ciliary dyskinesia on chromosome 5p and identification of the heavy dynein chain DNAH5 as a candidate gene. Am J Respir Cell Mol Biol. 2000;23:696-702 pubmed
    ..On the basis of the Chlamydomonas model for PCD, this gene represents an excellent candidate for PCD. ..
  9. Baker K, Beales P. Making sense of cilia in disease: the human ciliopathies. Am J Med Genet C Semin Med Genet. 2009;151C:281-95 pubmed publisher
    ..We review the common clinical phenotypes associated with ciliopathies and interrogate Online Mendelian Inheritance in Man (OMIM) to compile a comprehensive list of putative disorders in which ciliary dysfunction may play a role. ..

More Information


  1. Jorissen M, Willems T. Success rates of respiratory epithelial cell culture techniques with ciliogenesis for diagnosing primary ciliary dyskinesia. Acta Otorhinolaryngol Belg. 2000;54:357-65 pubmed
    ..In a total of 84 patients (10.3%) the final diagnosis was primary ciliary dyskinesia. Eighteen percent of the samples were considered normal, in 24% secondary ciliary dyskinesia was diagnosed. ..
  2. Davis E, Katsanis N. The ciliopathies: a transitional model into systems biology of human genetic disease. Curr Opin Genet Dev. 2012;22:290-303 pubmed publisher
  3. Meeks M, Walne A, Spiden S, Simpson H, Mussaffi Georgy H, Hamam H, et al. A locus for primary ciliary dyskinesia maps to chromosome 19q. J Med Genet. 2000;37:241-4 pubmed
    ..7. A 15 cM critical region is defined by recombinations at D19S572 and D19S218. These data provide significant evidence for a PCD locus on chromosome 19q and confirm locus heterogeneity. ..
  4. Jorissen M, Willems T. The secondary nature of ciliary (dis)orientation in secondary and primary ciliary dyskinesia. Acta Otolaryngol. 2004;124:527-31 pubmed
    ..Ciliary disorientation was never found as the single abnormality. COR can be considered to be secondary in PCD. Both ciliary (im)motility and SCD percentage contribute to COR. ..
  5. Sang L, Miller J, Corbit K, Giles R, Brauer M, Otto E, et al. Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways. Cell. 2011;145:513-28 pubmed publisher
    ..Our study further illustrates the power of linking proteomic networks and human genetics to uncover critical disease pathways. ..
  6. Arts H, Doherty D, van Beersum S, Parisi M, Letteboer S, Gorden N, et al. Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome. Nat Genet. 2007;39:882-8 pubmed
    ..This work identifies RPGRIP1L as a gene responsible for JBTS and establishes a central role for cilia and basal bodies in the pathophysiology of this disorder...
  7. O Callaghan C, Rutman A, Williams G, Hirst R. Inner dynein arm defects causing primary ciliary dyskinesia: repeat testing required. Eur Respir J. 2011;38:603-7 pubmed publisher
    ..Patients suspected of PCD due to an inner dynein arm defect or radial spoke defect should have the diagnosis reassessed if it has been based on only one diagnostic sample. ..
  8. Dowdle W, Robinson J, Kneist A, Sirerol Piquer M, Frints S, Corbit K, et al. Disruption of a ciliary B9 protein complex causes Meckel syndrome. Am J Hum Genet. 2011;89:94-110 pubmed publisher
    ..Our data indicate that B9d1 is required for normal Hh signaling, ciliogenesis, and ciliary protein localization and that B9d1 and B9d2 are essential components of a B9 protein complex, disruption of which causes MKS...
  9. Felix H, Holzmann D. Function and ultrastructure of cilia in primary ciliary dyskinesia. Schweiz Med Wochenschr. 2000;130:699-704 pubmed
    ..e. after ruling out the other well known causes) with "situs inversus". ..
  10. Adams M, Simms R, Abdelhamed Z, Dawe H, Szymanska K, Logan C, et al. A meckelin-filamin A interaction mediates ciliogenesis. Hum Mol Genet. 2012;21:1272-86 pubmed publisher
    ..Concurrent with these processes, the meckelin-filamin A signalling axis may be a key regulator in maintaining correct, normal levels of Wnt signalling. ..
  11. Delous M, Baala L, Salomon R, Laclef C, Vierkotten J, Tory K, et al. The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome. Nat Genet. 2007;39:875-81 pubmed
    ..Our findings show that mutations in RPGRIP1L can cause the multiorgan phenotypic abnormalities found in CORS or MKS, which therefore represent a continuum of the same underlying disorder...
  12. Coren M, Meeks M, Morrison I, Buchdahl R, Bush A. Primary ciliary dyskinesia: age at diagnosis and symptom history. Acta Paediatr. 2002;91:667-9 pubmed
  13. Jeganathan D, Chodhari R, Meeks M, Faeroe O, Smyth D, Nielsen K, et al. Loci for primary ciliary dyskinesia map to chromosome 16p12.1-12.2 and 15q13.1-15.1 in Faroe Islands and Israeli Druze genetic isolates. J Med Genet. 2004;41:233-40 pubmed
  14. Escudier E, Duquesnoy P, Papon J, Amselem S. Ciliary defects and genetics of primary ciliary dyskinesia. Paediatr Respir Rev. 2009;10:51-4 pubmed publisher
    ..The relative contribution of DNAI2 is currently being assessed. In all the other patients with ODA or other ultrastructural defects, the causative genes remain to be identified. ..
  15. Taschner M, Bhogaraju S, Lorentzen E. Architecture and function of IFT complex proteins in ciliogenesis. Differentiation. 2012;83:S12-22 pubmed publisher
    ..In this review we will give an update on the knowledge of the structure and function of individual IFT proteins, and the way these proteins interact to form the complex that facilitates IFT. ..
  16. Pennarun G, Escudier E, Chapelin C, Bridoux A, Cacheux V, Roger G, et al. Loss-of-function mutations in a human gene related to Chlamydomonas reinhardtii dynein IC78 result in primary ciliary dyskinesia. Am J Hum Genet. 1999;65:1508-19 pubmed
    ..These data reveal the critical role of DNAI1 in the development of human axonemal structures and open up new means for identification of additional genes involved in related developmental defects. ..
  17. Marthin J, Petersen N, Skovgaard L, Nielsen K. Lung function in patients with primary ciliary dyskinesia: a cross-sectional and 3-decade longitudinal study. Am J Respir Crit Care Med. 2010;181:1262-8 pubmed publisher
    ..Early diagnosis did not protect against decline in lung function. ..
  18. Novarino G, Akizu N, Gleeson J. Modeling human disease in humans: the ciliopathies. Cell. 2011;147:70-9 pubmed publisher
    ..Sitting at the interface between simple and complex genetic conditions, these diseases provide clues to the future direction of human genetics. ..
  19. Ikegami K, Sato S, Nakamura K, Ostrowski L, Setou M. Tubulin polyglutamylation is essential for airway ciliary function through the regulation of beating asymmetry. Proc Natl Acad Sci U S A. 2010;107:10490-5 pubmed publisher
    ..Our findings provide evidence that tubulin glutamylation is essential for ciliary function through the regulation of beating asymmetry, and provides insight into the molecular basis underlying the beating asymmetry. ..
  20. Olbrich H, Horvath J, Fekete A, Loges N, Storm van s Gravesande K, Blum A, et al. Axonemal localization of the dynein component DNAH5 is not altered in secondary ciliary dyskinesia. Pediatr Res. 2006;59:418-22 pubmed
    ..DNAH5 localization is not altered by SCD, indicating a high potential for immunofluorescence analysis as a novel diagnostic tool in PCD. ..
  21. Noone P, Bali D, Carson J, Sannuti A, Gipson C, Ostrowski L, et al. Discordant organ laterality in monozygotic twins with primary ciliary dyskinesia. Am J Med Genet. 1999;82:155-60 pubmed
    ..This is consistent with the hypothesis that situs inversus occurring in patients with primary ciliary dyskinesia is a random but "complete" event in the fetal development of patients with PCD. ..
  22. Guichard C, Harricane M, Lafitte J, Godard P, Zaegel M, Tack V, et al. Axonemal dynein intermediate-chain gene (DNAI1) mutations result in situs inversus and primary ciliary dyskinesia (Kartagener syndrome). Am J Hum Genet. 2001;68:1030-5 pubmed
    ..Finally, this study demonstrates a link between ciliary function and situs determination, since compound mutation heterozygosity in DNAI1 results in PCD with situs solitus or situs inversus (KS). ..
  23. Becker Heck A, Zohn I, Okabe N, Pollock A, Lenhart K, Sullivan Brown J, et al. The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation. Nat Genet. 2011;43:79-84 pubmed publisher
    ..CCDC40 localizes to motile cilia and the apical cytoplasm and is required for axonemal recruitment of CCDC39, disruption of which underlies a similar variant of PCD. ..
  24. Jorissen M, Willems T, Van Der Schueren B, Verbeken E, De Boeck K. Ultrastructural expression of primary ciliary dyskinesia after ciliogenesis in culture. Acta Otorhinolaryngol Belg. 2000;54:343-56 pubmed
    ..In conclusion, inherited abnormalities in primary ciliary dyskinesia are expressed after ciliogenesis, while secondary abnormalities are virtually absent, thereby facilitating the ultrastructural diagnosis. ..
  25. Geremek M, Witt M. Primary ciliary dyskinesia: genes, candidate genes and chromosomal regions. J Appl Genet. 2004;45:347-61 pubmed
    ..In this review, the disease pathomechanism is discussed along with the genes that are or may be involved in the pathogenesis of primary ciliary dyskinesia and the Kartagener syndrome. ..
  26. Vogel P, Hansen G, Fontenot G, Read R. Tubulin tyrosine ligase-like 1 deficiency results in chronic rhinosinusitis and abnormal development of spermatid flagella in mice. Vet Pathol. 2010;47:703-12 pubmed publisher
  27. Escudier E, Couprie M, Duriez B, Roudot Thoraval F, Millepied M, Prulière Escabasse V, et al. Computer-assisted analysis helps detect inner dynein arm abnormalities. Am J Respir Crit Care Med. 2002;166:1257-62 pubmed
    ..Computer-assisted analysis of ciliary micrographs improves the characterization of inherited axonemal defects. ..
  28. Williams C, Li C, Kida K, Inglis P, Mohan S, Semenec L, et al. MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function during ciliogenesis. J Cell Biol. 2011;192:1023-41 pubmed publisher
  29. Brugmann S, Cordero D, Helms J. Craniofacial ciliopathies: A new classification for craniofacial disorders. Am J Med Genet A. 2010;152A:2995-3006 pubmed publisher
    ..Finally, we propose that some non-classified disorders may now be classified as craniofacial ciliopathies...
  30. Zariwala M, Knowles M, Omran H. Genetic defects in ciliary structure and function. Annu Rev Physiol. 2007;69:423-50 pubmed
    ..Recent mutational analysis demonstrated that 38% of PCD patients carry mutations of the dynein genes DNAI1 and DNAH5. Increased understanding of the pathogenesis will aid in better diagnosis and treatment of PCD. ..
  31. Collin G, Won J, Hicks W, Cook S, Nishina P, Naggert J. Meckelin is necessary for photoreceptor intraciliary transport and outer segment morphogenesis. Invest Ophthalmol Vis Sci. 2012;53:967-74 pubmed publisher
    ..In this study, the retinal morphology and ciliary function in a mouse model for Meckel Syndrome Type 3 (MKS3) throughout the course of photoreceptor development was examined...
  32. Pifferi M, Montemurro F, Cangiotti A, Ragazzo V, Di Cicco M, Vinci B, et al. Simplified cell culture method for the diagnosis of atypical primary ciliary dyskinesia. Thorax. 2009;64:1077-81 pubmed publisher
    ..Culture of cells obtained with brushing of the nasal turbinate is not a perfect test, nevertheless it may offer diagnostic help in doubtful cases of PCD. ..
  33. Afzelius B. Cilia-related diseases. J Pathol. 2004;204:470-7 pubmed
    ..Ciliary malfunctions due to genetic errors tend to be systemic and life-long, whereas acquired diseases are local and may be temporary only. ..
  34. Tallila J, Jakkula E, Peltonen L, Salonen R, Kestila M. Identification of CC2D2A as a Meckel syndrome gene adds an important piece to the ciliopathy puzzle. Am J Hum Genet. 2008;82:1361-7 pubmed publisher
  35. Badano J, Mitsuma N, Beales P, Katsanis N. The ciliopathies: an emerging class of human genetic disorders. Annu Rev Genomics Hum Genet. 2006;7:125-48 pubmed
  36. Vincensini L, Blisnick T, Bastin P. 1001 model organisms to study cilia and flagella. Biol Cell. 2011;103:109-30 pubmed publisher
    ..For example, the function of genes involved in primary ciliary dyskinesia (due to defects in ciliary motility) can be efficiently assessed in trypanosomes. ..
  37. Katsuyama I, Arakawa T. A novel in vitro model for screening and evaluation of anti-asthenopia drugs. J Pharmacol Sci. 2003;93:222-4 pubmed
    ..Treatment of the repeatedly stimulated muscle with cyanocobalamin restored contraction dose-dependently. Thus, the model developed in this study can be used to screen drug candidates for treating asthenopia. ..
  38. Shaheen R, Faqeih E, Alshammari M, Swaid A, Al Gazali L, Mardawi E, et al. Genomic analysis of Meckel-Gruber syndrome in Arabs reveals marked genetic heterogeneity and novel candidate genes. Eur J Hum Genet. 2013;21:762-8 pubmed publisher
  39. Shelly M. The humidification and filtration functions of the airways. Respir Care Clin N Am. 2006;12:139-48 pubmed
    ..Studies of disorders mucus and ciliary function have improved the understanding of this forgotten organ. The clinical implications of this understanding have yet to be explored. ..
  40. Datta G, Dastidar D, Kundu S, Datta B, Dastidar N, Bannerjee A. A case of primary ciliary dyskinesia with pulmonary arterial hypertension responding to oral sildenafil. J Assoc Physicians India. 2011;59:738-40 pubmed
    ..Here we present a case of PCD with recurrent respiratory tract infections, bronchiectasis and severe PAH, who responded to treatment with Oxygen, IV broad spectrum antibiotics and oral sildenafil. ..
  41. Aguilar A, Meunier A, Strehl L, Martinovic J, Bonniere M, Attie Bitach T, et al. Analysis of human samples reveals impaired SHH-dependent cerebellar development in Joubert syndrome/Meckel syndrome. Proc Natl Acad Sci U S A. 2012;109:16951-6 pubmed publisher
    ..Our results, obtained from the analysis of human samples, show that the hemispheres and the vermis are affected in JS/MKS and provide evidence of a defective cellular mechanism in these pathologic processes...
  42. Al Belushi M, Al Ibrahim A, Ahmed M, Ahmed B, Khenyab N, Konje J. A review of Meckel-Gruber syndrome--incidence and outcome in the state of Qatar. J Matern Fetal Neonatal Med. 2016;29:2013-6 pubmed publisher
    ..We conclude that diagnosis in early pregnancy does not require the classical triad of encephalocele, polydactyly and polycystic kidneys as some of these features do not manifest on imaging until much later. ..
  43. Dogru D, Nik Ain A, Kiper N, Gocmen A, Ozcelik U, Yalcin E, et al. Bronchiectasis: the consequence of late diagnosis in chronic respiratory symptoms. J Trop Pediatr. 2005;51:362-5 pubmed
    ..Early diagnosis and treatment will increase the quality of life and survival of patients with bronchiectasis, which has irreversible and progressive complications if untreated. ..
  44. Zietkiewicz E, Nitka B, Voelkel K, Skrzypczak U, Bukowy Z, Rutkiewicz E, et al. Population specificity of the DNAI1 gene mutation spectrum in primary ciliary dyskinesia (PCD). Respir Res. 2010;11:174 pubmed publisher
    ..Results of the MLPA analysis indicate that no large exonic deletions are involved in PCD pathogenesis. ..
  45. Carraro S, Cutrone C, Cardarelli C, Zanconato S, Baraldi E. Clinical application of nasal nitric oxide measurement. Int J Immunopathol Pharmacol. 2010;23:50-2 pubmed
    ..Particularly low concentrations have been described in children with primary ciliary dyskinesia, so nNO measurement has been proposed as a reliable screening test for this chronic lung disease. ..
  46. Cayan S, Conaghan J, Schriock E, Ryan I, Black L, Turek P. Birth after intracytoplasmic sperm injection with use of testicular sperm from men with Kartagener/immotile cilia syndrome. Fertil Steril. 2001;76:612-4 pubmed
    ..One case resulted in the birth of normal healthy girl. With testicular sperm, successful oocyte fertilization after ICSI in couples with male Kartagener/immotile cilia syndrome is possible despite the lack of sperm motility. ..
  47. Holzmann D, Ott P, Felix H. Diagnostic approach to primary ciliary dyskinesia: a review. Eur J Pediatr. 2000;159:95-8 pubmed
    ..The combination of extensive clinical examination with functional and ultrastructural analysis of the cilia results in a high degree of accuracy in diagnosing PCD. ..
  48. Casey B. Two rights make a wrong: human left-right malformations. Hum Mol Genet. 1998;7:1565-71 pubmed
  49. Hopp K, Heyer C, Hommerding C, Henke S, Sundsbak J, Patel S, et al. B9D1 is revealed as a novel Meckel syndrome (MKS) gene by targeted exon-enriched next-generation sequencing and deletion analysis. Hum Mol Genet. 2011;20:2524-34 pubmed publisher
    ..The fetus inherited an additional likely pathogenic novel missense change to a second MKS gene, CEP290; p.R2210C, suggesting oligogenic inheritance in this disorder. ..
  50. Monini S, Torrisi M, Eliseo I, Visco V, Raffa S, Bandiera G, et al. Ultrastructural ciliary findings in nasal obstructive diseases. Rhinology. 2005;43:251-6 pubmed
    ..According to the findings derived from this study, mechanical nasal obstruction seems to cause major alterations on the nasal ciliary arrangement, thus determining a functional impairment on the whole nasal function. ..
  51. Corbelli R, Bringolf Isler B, Amacher A, Sasse B, Spycher M, Hammer J. Nasal nitric oxide measurements to screen children for primary ciliary dyskinesia. Chest. 2004;126:1054-9 pubmed
    ..The measurement of nasal NO appears to be a useful tool to screen children for PCD and to exclude this disease in those with high nasal NO levels. ..
  52. Bertrand B, Collet S, Eloy P, Rombaux P. Secondary ciliary dyskinesia in upper respiratory tract. Acta Otorhinolaryngol Belg. 2000;54:309-16 pubmed
    ..To distinct from ultrastructural images between primary and secondary ciliary dyskinesia is often uneasy because some of the findings in secondary ciliary dyskinesia obviously mimic those dedicated to primary ciliary dyskinesia. ..
  53. Chodhari R, Mitchison H, Meeks M. Cilia, primary ciliary dyskinesia and molecular genetics. Paediatr Respir Rev. 2004;5:69-76 pubmed
    ..This may also allow the development of new methods for diagnosis, prevention and treatment of PCD. ..