{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:28:25Z","timestamp":1791286105824,"version":"4.1.0"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2011,9,1]],"date-time":"2011-09-01T00:00:00Z","timestamp":1314835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The ciliopathies are a category of diseases caused by disruption of the physiological functions of cilia. Ciliary dysfunction results in a broad range of phenotypes, including renal, hepatic, and pancreatic cyst formation; situs abnormalities; retinal degeneration; anosmia; cerebellar or other brain anomalies; postaxial polydactyly; bronchiectasis; and infertility. The specific clinical features are dictated by the subtype, structure, distribution, and function of the affected cilia. This review highlights the clinical variability caused by dysfunction of motile and nonmotile primary cilia and emphasizes the genetic heterogeneity and phenotypic overlap that are characteristics of these disorders. There is a need for additional research to understand the shared and unique functions of motile and nonmotile cilia and the pathophysiology resulting from mutations in cilia, basal bodies, or centrosomes. Increased understanding of ciliary biology will improve the diagnosis and management of primary ciliary dyskinesia, syndromic ciliopathies, and cilia-related cystic diseases.<\/jats:p>","DOI":"10.1513\/pats.201103-025sd","type":"journal-article","created":{"date-parts":[[2011,9,16]],"date-time":"2011-09-16T20:11:10Z","timestamp":1316203870000},"page":"444-450","source":"Crossref","is-referenced-by-count":96,"title":["Spectrum of Clinical Diseases Caused By Disorders of Primary Cilia"],"prefix":"10.1093","volume":"8","author":[{"given":"Stephanie M.","family":"Ware","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meral Gunay-","family":"Aygun","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedhelm","family":"Hildebrandt","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,9,15]]},"reference":[{"key":"2026020502114492300_bib1","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/nrm2278","article-title":"When cilia go bad: cilia defects and ciliopathies","volume":"8","author":"Fliegauf","year":"2007","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2026020502114492300_bib2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1080\/13816810701537424","article-title":"The retinal ciliopathies","volume":"28","author":"Adams","year":"2007","journal-title":"Ophthalmic Genet"},{"key":"2026020502114492300_bib3","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/j.1600-0854.2006.00516.x","article-title":"Sensory cilia and integration of signal transduction in human health and disease","volume":"8","author":"Christensen","year":"2007","journal-title":"Traffic"},{"key":"2026020502114492300_bib4","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1002\/ajmg.c.30227","article-title":"Ciliary biology: understanding the cellular and genetic basis of human ciliopathies","volume":"151C","author":"Cardenas-Rodriguez","year":"2009","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2026020502114492300_bib5","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1126\/science.1124534","article-title":"The primary cilium as the cell's antenna: signaling at a sensory organelle","volume":"313","author":"Singla","year":"2006","journal-title":"Science"},{"key":"2026020502114492300_bib6","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/j.1399-0004.2009.01305.x","article-title":"Ciliary dysfunction and obesity","volume":"77","author":"Mok","year":"2010","journal-title":"Clin Genet"},{"key":"2026020502114492300_bib7","doi-asserted-by":"crossref","first-page":"S71","DOI":"10.1111\/j.1440-169X.2008.01008.x","article-title":"Breakthroughs and future challenges in left-right patterning","volume":"50","author":"Hamada","year":"2008","journal-title":"Dev Growth Differ"},{"key":"2026020502114492300_bib8","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.mod.2004.08.006","article-title":"Left-right asymmetry in embryonic development: a comprehensive review","volume":"122","author":"Levin","year":"2005","journal-title":"Mech Dev"},{"key":"2026020502114492300_bib9","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/sj.ejhg.5201506","article-title":"Genetics of human heterotaxias","volume":"14","author":"Zhu","year":"2006","journal-title":"Eur J Hum Genet"},{"key":"2026020502114492300_bib10","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/S0002-9149(99)00849-8","article-title":"Extracardiac anomalies in the heterotaxy syndromes with focus on anomalies of midline-associated structures","volume":"85","author":"Ticho","year":"2000","journal-title":"Am J Cardiol"},{"key":"2026020502114492300_bib11","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1086\/380998","article-title":"Identification and functional analysis of zic3 mutations in heterotaxy and related congenital heart defects","volume":"74","author":"Ware","year":"2004","journal-title":"Am J Hum Genet"},{"key":"2026020502114492300_bib12","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1002\/tera.10099","article-title":"Risk factors for heart disease associated with abnormal sidedness","volume":"66","author":"Kuehl","year":"2002","journal-title":"Teratology"},{"key":"2026020502114492300_bib13","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/ajmg.c.30228","article-title":"Disorders of left-right asymmetry: heterotaxy and situs inversus","volume":"151C","author":"Sutherland","year":"2009","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2026020502114492300_bib14","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1242\/dev.129.9.2293","article-title":"A complex syndrome of left-right axis, central nervous system and axial skeleton defects in zic3 mutant mice","volume":"129","author":"Purandare","year":"2002","journal-title":"Development"},{"key":"2026020502114492300_bib15","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1002\/dvdy.20719","article-title":"Heart defects in x\u2013linked heterotaxy: evidence for a genetic interaction of zic3 with the nodal signaling pathway","volume":"235","author":"Ware","year":"2006","journal-title":"Dev Dyn"},{"key":"2026020502114492300_bib16","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1002\/dvdy.20668","article-title":"Zic3 is critical for early embryonic patterning during gastrulation","volume":"235","author":"Ware","year":"2006","journal-title":"Dev Dyn"},{"key":"2026020502114492300_bib17","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1093\/hmg\/ddn411","article-title":"Identification and functional characterization of nodal rare variants in heterotaxy and isolated cardiovascular malformations","volume":"18","author":"Mohapatra","year":"2009","journal-title":"Hum Mol Genet"},{"key":"2026020502114492300_bib18","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1086\/339079","article-title":"Cfc1 mutations in patients with transposition of the great arteries and double-outlet right ventricle","volume":"70","author":"Goldmuntz","year":"2002","journal-title":"Am J Hum Genet"},{"key":"2026020502114492300_bib19","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ajhg.2008.05.012","article-title":"Reduced nodal signaling strength via mutation of several pathway members including foxh1 is linked to human heart defects and holoprosencephaly","volume":"83","author":"Roessler","year":"2008","journal-title":"Am J Hum Genet"},{"key":"2026020502114492300_bib20","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1002\/ajmg.c.30225","article-title":"Liver and kidney disease in ciliopathies","volume":"151C","author":"Gunay-Aygun","year":"2009","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2026020502114492300_bib21","article-title":"Congenital hepatic fibrosis overview","author":"Gunay-Aygun","year":"2008"},{"key":"2026020502114492300_bib22","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1002\/hep.1840160434","article-title":"Congenital diseases of intrahepatic bile ducts: variations on the theme \u201cductal plate malformation\u201d","volume":"16","author":"Desmet","year":"1992","journal-title":"Hepatology"},{"key":"2026020502114492300_bib23","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/sj.ejhg.5201648","article-title":"Joubert syndrome (and related disorders) (omim 213300)","volume":"15","author":"Parisi","year":"2007","journal-title":"Eur J Hum Genet"},{"key":"2026020502114492300_bib24","article-title":"Bardet-biedl syndrome [accessed March 10, 2011]. GeneReviews","author":"Beales","year":"2007"},{"key":"2026020502114492300_bib25","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.5858\/2006-130-1236-MS","article-title":"Meckel-gruber syndrome: pathologic manifestations, minimal diagnostic criteria, and differential diagnosis","volume":"130","author":"Alexiev","year":"2006","journal-title":"Arch Pathol Lab Med"},{"key":"2026020502114492300_bib26","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.1002\/ajmg.a.33666","article-title":"Fibrocystic disease of liver and pancreas; under-recognized features of the x\u2013linked ciliopathy oral-facial-digital syndrome type 1 (ofd i)","volume":"152A","author":"Chetty-John","year":"2010","journal-title":"Am J Med Genet A"},{"key":"2026020502114492300_bib27","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1002\/ajmg.a.32962","article-title":"Clinical variability of asphyxiating thoracic dystrophy (jeune) syndrome: evaluation and classification of 13 patients","volume":"149A","author":"Tuysuz","year":"2009","journal-title":"Am J Med Genet A"},{"key":"2026020502114492300_bib28","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/ajmg.c.30226","article-title":"Ellis-van creveld syndrome and weyers acrodental dysostosis are caused by cilia-mediated diminished response to hedgehog ligands","volume":"151C","author":"Ruiz-Perez","year":"2009","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2026020502114492300_bib29","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1002\/ajmg.a.31464","article-title":"Sensenbrenner syndrome: a new member of the hepatorenal fibrocystic family","volume":"140","author":"Zaffanello","year":"2006","journal-title":"Am J Med Genet A"},{"key":"2026020502114492300_bib30","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1097\/GIM.0b013e3181a02882","article-title":"The nonmotile ciliopathies","volume":"11","author":"Tobin","year":"2009","journal-title":"Genet Med"},{"key":"2026020502114492300_bib31","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.jpeds.2009.03.045","article-title":"Mks3-related ciliopathy with features of autosomal recessive polycystic kidney disease, nephronophthisis, and joubert syndrome","volume":"155","author":"Gunay-Aygun","year":"2009","journal-title":"J Pediatr"},{"key":"2026020502114492300_bib32","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/ng1097-149","article-title":"A novel gene encoding an sh3 domain protein is mutated in nephronophthisis type 1","volume":"17","author":"Hildebrandt","year":"1997","journal-title":"Nat Genet"},{"key":"2026020502114492300_bib33","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/ng1217","article-title":"Mutations in invs encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination","volume":"34","author":"Otto","year":"2003","journal-title":"Nat Genet"},{"key":"2026020502114492300_bib34","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/ng0803-355","article-title":"From cilia to cyst","volume":"34","author":"Watnick","year":"2003","journal-title":"Nat Genet"},{"key":"2026020502114492300_bib35","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1038\/nrg1727","article-title":"Cilia and centrosomes: a unifying pathogenic concept for cystic kidney disease?","volume":"6","author":"Hildebrandt","year":"2005","journal-title":"Nat Rev Genet"},{"key":"2026020502114492300_bib36","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/ng1216","article-title":"Mutations in a novel gene, nphp3, cause adolescent nephronophthisis, tapeto-retinal degeneration and hepatic fibrosis","volume":"34","author":"Olbrich","year":"2003","journal-title":"Nat Genet"},{"key":"2026020502114492300_bib37","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1038\/nm935","article-title":"Inhibition of renal cystic disease development and progression by a vasopressin v2 receptor antagonist","volume":"9","author":"Gattone","year":"2003","journal-title":"Nat Med"},{"key":"2026020502114492300_bib38","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1086\/344395","article-title":"A gene mutated in nephronophthisis and retinitis pigmentosa encodes a novel protein, nephroretinin, conserved in evolution","volume":"71","author":"Otto","year":"2002","journal-title":"Am J Hum Genet"},{"key":"2026020502114492300_bib39","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1681\/ASN.2003121025","article-title":"Expression and phenotype analysis of the nephrocystin-1 and nephrocystin-4 homologs in caenorhabditis elegans","volume":"16","author":"Wolf","year":"2005","journal-title":"J Am Soc Nephrol"},{"key":"2026020502114492300_bib40","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/ng1520","article-title":"Nephrocystin-5, a ciliary iq domain protein, is mutated in senior-loken syndrome and interacts with rpgr and calmodulin","volume":"37","author":"Otto","year":"2005","journal-title":"Nat Genet"},{"key":"2026020502114492300_bib41","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1038\/ng1644","article-title":"Disruption of bardet-biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates","volume":"37","author":"Ross","year":"2005","journal-title":"Nat Genet"},{"key":"2026020502114492300_bib42","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/ng1552","article-title":"Inversin, the gene product mutated in nephronophthisis type ii, functions as a molecular switch between wnt signaling pathways","volume":"37","author":"Simons","year":"2005","journal-title":"Nat Genet"},{"key":"2026020502114492300_bib43","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/ng1701","article-title":"Defective planar cell polarity in polycystic kidney disease","volume":"38","author":"Fischer","year":"2006","journal-title":"Nat Genet"},{"key":"2026020502114492300_bib44","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/nature02061","article-title":"Hedgehog signalling in the mouse requires intraflagellar transport proteins","volume":"426","author":"Huangfu","year":"2003","journal-title":"Nature"},{"key":"2026020502114492300_bib45","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/ng1786","article-title":"The centrosomal protein nephrocystin-6 is mutated in joubert syndrome and activates transcription factor atf4","volume":"38","author":"Sayer","year":"2006","journal-title":"Nat Genet"},{"key":"2026020502114492300_bib46","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1093\/hmg\/ddl107","article-title":"In-frame deletion in a novel centrosomal\/ciliary protein cep290\/nphp6 perturbs its interaction with rpgr and results in early-onset retinal degeneration in the rd16 mouse","volume":"15","author":"Chang","year":"2006","journal-title":"Hum Mol Genet"},{"key":"2026020502114492300_bib47","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1086\/507318","article-title":"Mutations in the cep290 (nphp6) gene are a frequent cause of leber congenital amaurosis","volume":"79","author":"den Hollander","year":"2006","journal-title":"Am J Hum Genet"},{"key":"2026020502114492300_bib48","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1038\/ng2072","article-title":"Loss of glis2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis","volume":"39","author":"Attanasio","year":"2007","journal-title":"Nat Genet"},{"key":"2026020502114492300_bib49","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/ng2039","article-title":"The ciliary gene rpgrip1l is mutated in cerebello-oculo-renal syndrome (joubert syndrome type b) and meckel syndrome","volume":"39","author":"Delous","year":"2007","journal-title":"Nat Genet"},{"key":"2026020502114492300_bib50","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1681\/ASN.2007040490","article-title":"Nek8 mutations affect ciliary and centrosomal localization and may cause nephronophthisis","volume":"19","author":"Otto","year":"2008","journal-title":"J Am Soc Nephrol"},{"key":"2026020502114492300_bib51","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/ng.756","article-title":"Ttc21b contributes both causal and modifying alleles across the ciliopathy spectrum","volume":"43","author":"Davis","year":"2011","journal-title":"Nat Genet"},{"key":"2026020502114492300_bib52","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1126\/science.1173869","article-title":"Motile cilia of human airway epithelia are chemosensory","volume":"325","author":"Shah","year":"2009","journal-title":"Science"},{"key":"2026020502114492300_bib53","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1242\/jcs.066308","article-title":"Sensory reception is an attribute of both primary cilia and motile cilia","volume":"123","author":"Bloodgood","year":"2010","journal-title":"J Cell Sci"},{"key":"2026020502114492300_bib54","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1136\/jmg.2010.077883","article-title":"Abnormal respiratory cilia in non-syndromic leber congenital amaurosis with cep290 mutations","volume":"47","author":"Papon","year":"2010","journal-title":"J Med Genet"},{"key":"2026020502114492300_bib55","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1378\/chest.07-2147","article-title":"Autosomal dominant polycystic kidney disease is associated with an increased prevalence of radiographic bronchiectasis","volume":"133","author":"Driscoll","year":"2008","journal-title":"Chest"},{"key":"2026020502114492300_bib56","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1161\/CIRCULATIONAHA.106.649038","article-title":"Congenital heart disease and other heterotaxic defects in a large cohort of patients with primary ciliary dyskinesia","volume":"115","author":"Kennedy","year":"2007","journal-title":"Circulation"},{"key":"2026020502114492300_bib57","doi-asserted-by":"crossref","first-page":"2915","DOI":"10.1073\/pnas.1019645108","article-title":"Rare copy number variations in congenital heart disease patients identify unique genes in left-right patterning","volume":"108","author":"Fakhro","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026020502114492300_bib58","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s00439-010-0902-8","article-title":"Mutation analysis in bardet-biedl syndrome by DNA pooling and massively parallel resequencing in 105 individuals","volume":"129","author":"Janssen","year":"2011","journal-title":"Hum Genet"},{"key":"2026020502114492300_bib59","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1136\/jmg.2010.082552","article-title":"Mutation analysis of 18 nephronophthisis associated ciliopathy disease genes using a DNA pooling and next generation sequencing strategy","volume":"48","author":"Otto","year":"2011","journal-title":"J Med Genet"},{"key":"2026020502114492300_bib60","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1038\/ng.662","article-title":"Candidate exome capture identifies mutation of sdccag8 as the cause of a retinal-renal ciliopathy","volume":"42","author":"Otto","year":"2010","journal-title":"Nat Genet"}],"container-title":["Proceedings of the American Thoracic Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/annalsats\/article-pdf\/8\/5\/444\/66578855\/annalsats_8_5_444.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/annalsats\/article-pdf\/8\/5\/444\/66578855\/annalsats_8_5_444.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T07:12:07Z","timestamp":1770275527000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/annalsats\/article\/8\/5\/444\/8441130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,9]]},"references-count":60,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2011,9,15]]},"published-print":{"date-parts":[[2011,9,15]]}},"URL":"https:\/\/doi.org\/10.1513\/pats.201103-025sd","relation":{},"ISSN":["1546-3222","1943-5665"],"issn-type":[{"value":"1546-3222","type":"print"},{"value":"1943-5665","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,9]]},"published":{"date-parts":[[2011,9]]}}}