Medicine:Ciliopathy

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Short description: Genetic disease resulting in abnormal formation or function of cilia

Ciliopathy
Eukaryotic cilium

Ciliopathies are a group of genetically diverse disorders involving defects in the structure or function of the primary cilium, a highly specialized and evolutionarily conserved organelle found in nearly all eukaryotic cells.[1] The primary cilium plays a central role in regulating signal transduction, making it essential for numerous developmental and physiological processes.[2]

Because of the widespread presence of primary cilia in different tissues, dysfunction can lead to a broad spectrum of clinical features. Syndromic ciliopathies, such as Bardet-Biedl syndrome (BBS), typically involve multiple organ systems, including the retina, kidneys, central nervous system, and skeletal system[1] These manifestations highlight the importance of cilia in embryonic development, sensory perception, and tissue homeostasis.[3]

The genetic basis of ciliopathies is complex, with significant allelic heterogeneity and pleiotropy, meaning the same gene may cause different disorders, while different mutations can result in overlapping clinical features. Such variability makes genotype-phenotype correlation particularly challenging.[1][4] Advances in genetic technologies, such as expression quantitative trait locus (eQTL) analysis, are helping to clarify the molecular mechanisms that drive these diseases. While progress has been made in understanding ciliogenesis and the molecular pathways involved, therapeutic development is still in its early stages. Gene therapy and other molecular approaches hold promise but must overcome several scientific and technical barriers before they can be widely implemented.[1]

Primary cilia, which are found on nearly all cell types, function as sensory structures and integrate signals from the environment. When these functions are compromised, it can lead to serious diseases such as polycystic kidney disease, Bardet-Biedl syndrome, Joubert syndrome, and primary ciliary dyskinesia.[3] Even proteins that are not directly localized to the cilia, such as XPNPEP3—which is associated with mitochondria—can cause ciliopathies by affecting proteins essential to ciliary function.[1]

In the 1990s, important advances were made in understanding the significance of cilia.[5] Ciliary defects were identified in genetic disorders such as nephronophthisis and primary ciliary dyskinesia, and it became clear that abnormalities in ciliary structure and transport mechanisms could explain the broad, multi-organ effects observed in patients with ciliopathies.[1][3]

Although our understanding of the role of cilia in developmental biology and disease has grown considerably over the past decade, the mechanisms behind their function in many tissues remain incompletely described. Current research is particularly focused on how disruptions in intraflagellar transport, signal reception, and cilia-associated protein complexes contribute to the pathogenesis of ciliopathies.[3][4]

Signs and symptoms

A wide variety of symptoms are potential clinical features of ciliopathy. The signs most exclusive to a ciliopathy, in descending order of exclusivity, are:[6]: 138 

A case with polycystic ovary syndrome, multiple subcutaneous cysts, renal function impairment, Caroli disease and liver cirrhosis due to ciliopathy has been described.[7]

Phenotypes sometimes associated with ciliopathies can include:

Although significant progress has been made in understanding cilia and their role in disease, many aspects remain unexplored. Ongoing research is crucial to uncover the underlying mechanisms of ciliopathies and to develop effective therapeutic strategies.[9][10]

Pathophysiology

Eukaryotic cilium, showing the axoneme arrangement of motile and non-motile (primary) cilia

Cilia are microscopic, hair-like structures that extend from the surface of nearly all mammalian cells. They are composed of complex protein structures and play a crucial role in various cellular functions, including movement and signal transduction.[11]

Cilia are categorized into two main structural subtypes based on the organization of their microtubule axoneme: motile and non-motile (primary) cilia. Motile cilia are typically structured in a 9+2 arrangement, consisting of nine outer microtubule doublets surrounding a central pair of microtubules.[11] This structure is specialized for movement, enabling functions such as fluid transport across epithelial surfaces, cell motility, and propulsion of spermatozoa.[12][13]

In contrast, primary (non-motile) cilia display a 9+0 arrangement, where nine outer microtubule doublets are present without a central pair. Rather than generating movement, these cilia serve as cellular antennae, playing crucial roles in sensory perception, intracellular signaling, and regulation of developmental pathways, including organogenesis.[11] Primary cilia function mainly as sensory organelles, involved in signal transduction and the maintenance of cellular homeostasis.[14]

This structural distinction is fundamental to understanding the diverse biological functions and pathologies associated with ciliopathies.[1]

Genetics

Ciliopathies are genetically heterogeneous disorders that arise due to mutations in genes associated with the structure and function of cilia. A unique feature of these conditions is that the same gene can be involved in different diseases, and that different genes can lead to similar phenotypes.[15] For example, mutations in certain genes have been linked to both Meckel–Gruber syndrome and Bardet–Biedl syndrome, and in some patients carrying mutations in both, combined phenotypes have been observed that do not occur in either condition alone.[1]

Because ciliopathy genes often function within interconnected developmental pathways, systems biologists are seeking to define gene modules—co-regulated sets of genes that drive specific biological outcomes.[1][4]

Furthermore, significant phenotypic overlap has been documented among different ciliopathies, largely due to the fact that many of the involved genes affect primary cilia function.[15] As a result, the same mutation can lead to different clinical presentations, suggesting that genetic modifiers (i.e., other genes that influence disease expression) play an important role in determining disease severity and organ involvement.[3][10] As of 2017, 187 genes had been confirmed to be directly associated with ciliopathies, with an additional 241 candidate genes still under investigation.[3]

This genetic complexity makes molecular diagnosis both challenging and essential. For inherited ciliopathies such as autosomal dominant and autosomal recessive polycystic kidney disease (ADPKD and ARPKD), traditional methods like linkage analysis and targeted mutation screening have been used.[3] Modern approaches such as gene panels, exome sequencing, and whole genome sequencing are increasingly replacing traditional methods, as they enable the identification of both known and rare mutations and can detect heterozygous carriers in recessive disorders.[3] These methods allow for broader detection of both common and rare mutations and are particularly useful for identifying heterozygous carriers in recessive ciliopathies. By providing a more comprehensive genetic profile, these tools enhance diagnostic precision and support the identification of novel ciliopathy-associated genes.[1][3]

A classic example of a genetically defined ciliopathy is ADPKD, which is caused by mutations in PKD1 and PKD2, encoding polycystin-1 and -2, respectively. These proteins are essential for the mechanosensory function of cilia in the renal epithelium. Mutations result in defective signaling and cyst formation, which can eventually lead to kidney failure.[1][4][10]

List of ciliopathies

This is a dynamic list and may never be able to satisfy particular standards for completeness. You can help by expanding it with reliably sourced entries.

Known ciliopathies

Condition OMIM Gene(s) Notes
Alström syndrome[6][16][17] Online Mendelian Inheritance in Man (OMIM) 203800 ALMS1[17]
Asphyxiating thoracic dysplasia (Jeune syndrome)[6][17][18] Online Mendelian Inheritance in Man (OMIM) 208500 DYNC2H1,[17] IFT80,[17] IFT139,[17] IFT140,[17] IFT144,[17] WDR35[17]
Bardet–Biedl syndrome[6][19][8][17] Online Mendelian Inheritance in Man (OMIM) 209900 ARL6,[17] BBS1,[17] BBS2,[17] BBS4,[17] BBS5,[17] BBS7,[17] BBS9,[17] BBS10,[17] BBS12,[17] MKKS,[17] MKS1,[17] MKS3,[17] SDCCAG8,[17] TTC8, TRIM32,[17] WDPCP[17]
Ellis–van Creveld syndrome[18][17] Online Mendelian Inheritance in Man (OMIM) 225500 EVC,[17] EVC2[17]
Joubert syndrome[6][8][17] Online Mendelian Inheritance in Man (OMIM) 213300 AHI1,[17] ATXN10,[17] ARL13B,[17] BRCC3, C5ORF42,[17] CC2D2A,[17] CEP41,[17] CEP290,[17] CORS2,[17] INPP5E,[17] JBTS1,[17] JBTS3,[17] JBTS4,[17] KIF7,[17] NPHP1,[17] NPHP3,[17] RPGRIP1L,[17] TCTN1,[17] TCTN2,[17] TMEM67,[17] TMEM138,[17] TMEM216,[17] TMEM237[17]
Leber congenital amaurosis[18] Online Mendelian Inheritance in Man (OMIM) 204000 GUCY2D, RPE65
McKusick–Kaufman syndrome[18] Online Mendelian Inheritance in Man (OMIM) 236700 MKKS
Meckel–Gruber syndrome[6][17][8][20] Online Mendelian Inheritance in Man (OMIM) 249000 B9D1,[17] B9D2,[17] CC2D2A,[17] CEP290,[17] MKS1-6,[17] MKKS,[17] NPHP3,[17] RPGRIP1L,[17] TCTN2,[17] TMEM67,[17] TMEM216[17]
Nephronophthisis[6][19][8][17] Online Mendelian Inheritance in Man (OMIM) 256100 ALMS1,[17] ATXN10,[17] CEP290,[17] GLIS2,[17] IFT139,[17] INVS,[17] IQCB1, NEK8,[17] NPHP1-11,[17] RPGRIP1L, TCTN2,[17] TTC21B,[17] TTC8,[17] WDR19,[17] XPNPEP3[17]
Orofaciodigital syndrome 1[16][19][17] Online Mendelian Inheritance in Man (OMIM) 311200 OFD1[17]
Polycystic kidney disease[6][19][17] (ADPKD and ARPKD)[21] Online Mendelian Inheritance in Man (OMIM) 173900 PKD1, PKD2, PKHD1[17]
Primary ciliary dyskinesia (Kartagener syndrome)[6] Online Mendelian Inheritance in Man (OMIM) 244400 DNAI1, DNAH5, TXNDC3, DNAH11, DNAI2, KTU, RSPH4A, RSPH9, LRRC50
Senior–Løken syndrome[19] Online Mendelian Inheritance in Man (OMIM) 266900 NPHP1, NPHP4, IQCB1, CEP290, SDCCAG8
Sensenbrenner syndrome (cranioectodermal dysplasia)[18] Online Mendelian Inheritance in Man (OMIM) 218330 IFT122
Short rib–polydactyly syndrome[18] Online Mendelian Inheritance in Man (OMIM) 613091 DYNC2H1
? ? IFT88 Novel form of congenital anosmia, reported in 2012[22]

Likely ciliopathies

Condition OMIM Gene(s) Notes
Acrocallosal syndrome[18] Online Mendelian Inheritance in Man (OMIM) 200990 KIF7, GLI3
Acromelic frontonasal dysostosis[18] Online Mendelian Inheritance in Man (OMIM) 603671 ZSWIM6
Arima syndrome[18] Online Mendelian Inheritance in Man (OMIM) 243910
Biemond syndrome[18] Online Mendelian Inheritance in Man (OMIM) 113400
COACH syndrome[18] Online Mendelian Inheritance in Man (OMIM) 216360 TMEM67, CC2D2A, RPGRIP1L
Conorenal syndrome[23][18] Online Mendelian Inheritance in Man (OMIM) 266920
Greig cephalopolysyndactyly syndrome[18] Online Mendelian Inheritance in Man (OMIM) 175700 GLI3
Hydrolethalus syndrome[18] Online Mendelian Inheritance in Man (OMIM) 236680 HYLS1
Johanson–Blizzard syndrome[18] Online Mendelian Inheritance in Man (OMIM) 243800 UBR1
Mohr syndrome (oral-facial-digital syndrome type 2)[18] Online Mendelian Inheritance in Man (OMIM) 252100
Neu–Laxova syndrome[18] Online Mendelian Inheritance in Man (OMIM) 256520 PHGDH, PSAT1, PSPH
Opitz G/BBB syndrome[18] Online Mendelian Inheritance in Man (OMIM) 300000 MID1
Pallister–Hall syndrome[18] Online Mendelian Inheritance in Man (OMIM) 146510 GLI3
Papillorenal syndrome[18] Online Mendelian Inheritance in Man (OMIM) 120330 PAX2
Renal–hepatic–pancreatic dysplasia[18] Online Mendelian Inheritance in Man (OMIM) 208540 NPHP3
Varadi–Papp syndrome (oral-facial-digital syndrome type 6)[18] Online Mendelian Inheritance in Man (OMIM) 277170

Possible ciliopathies

Condition OMIM Gene(s) Notes
Acrofacial dysostosis[18]
Acrofrontofacionasal dysostosis 2[18] Online Mendelian Inheritance in Man (OMIM) 239710
Adams–Oliver syndrome[18] Online Mendelian Inheritance in Man (OMIM) 100300 ARHGAP31, DOCK6, RBPJ, EOGT, NOTCH1, DLL4
Asplenia with cardiovascular anomalies (Ivemark syndrome)[18] Online Mendelian Inheritance in Man (OMIM) 208530
Autosomal recessive spastic paraplegia[18]
Barakat syndrome (HDR syndrome)[18] Online Mendelian Inheritance in Man (OMIM) 146255 GATA3
Basal cell nevus syndrome[18] Online Mendelian Inheritance in Man (OMIM) 109400 PTCH1, PTCH2, SUFU
Branchio‐oculo‐facial syndrome[18] Online Mendelian Inheritance in Man (OMIM) 113620 TFAP2A
C syndrome (Opitz trigonocephaly)[18] Online Mendelian Inheritance in Man (OMIM) 211750 CD96
Carpenter syndrome[18] Online Mendelian Inheritance in Man (OMIM) 201000 RAB23
Cephaloskeletal dysplasia (microcephalic osteodysplastic primordial dwarfism type 1)[18] Online Mendelian Inheritance in Man (OMIM) 210710 RNU4ATAC
Cerebrofaciothoracic dysplasia[18] Online Mendelian Inheritance in Man (OMIM) 213980 TMCO1
Cerebrofrontofacial syndrome (Baraitser–Winter syndrome)[18] Online Mendelian Inheritance in Man (OMIM) 243310 ACTB
Cerebrooculonasal syndrome[18] Online Mendelian Inheritance in Man (OMIM) 605627
Autosomal recessive spastic ataxia of Charlevoix-Saguenay[18] Online Mendelian Inheritance in Man (OMIM) 270550 SACS
Chondrodysplasia punctata 2[18] Online Mendelian Inheritance in Man (OMIM) 302960 EBP
Choroideremia[18] Online Mendelian Inheritance in Man (OMIM) 303100 CHM
Chudley–McCullough syndrome[18] Online Mendelian Inheritance in Man (OMIM) 604213 GPSM2
C‐like syndrome[18] Online Mendelian Inheritance in Man (OMIM) 605039 ASXL1
Coffin–Siris syndrome[18] Online Mendelian Inheritance in Man (OMIM) 135900 ARID1B, SOX11, ARID2
Cohen syndrome[18] Online Mendelian Inheritance in Man (OMIM) 216550 VPS13B
Craniofrontonasal dysplasia[18] Online Mendelian Inheritance in Man (OMIM) 304110 EFNB1
Dysgnathia complex[18] Online Mendelian Inheritance in Man (OMIM) 202650
Ectrodactyly–ectodermal dysplasia–cleft syndrome type 1[18] Online Mendelian Inheritance in Man (OMIM) 129900
Endocrine–cerebroosteodysplasia syndrome[18] Online Mendelian Inheritance in Man (OMIM) 612651 ICK
Focal dermal hypoplasia[18] Online Mendelian Inheritance in Man (OMIM) 305600 PORCN
Frontonasal dysplasia[18] Online Mendelian Inheritance in Man (OMIM) 136760 ALX3, ALX4, ALX1
Fryns microphthalmia syndrome[18] Online Mendelian Inheritance in Man (OMIM) 600776
Fryns syndrome[18] Online Mendelian Inheritance in Man (OMIM) 229850
Genitopatellar syndrome[18] Online Mendelian Inheritance in Man (OMIM) 606170 KAT6B
Hemifacial microsomia[18] Online Mendelian Inheritance in Man (OMIM) 164210
Hypothalamic hamartomas[18] Online Mendelian Inheritance in Man (OMIM) 241800
Johnson neuroectodermal syndrome[18] Online Mendelian Inheritance in Man (OMIM) 147770
Juvenile myoclonic epilepsy[24] Online Mendelian Inheritance in Man (OMIM) 254770
Kabuki syndrome[18] Online Mendelian Inheritance in Man (OMIM) 147920 KMT2D, KDM6A
Kallmann syndrome[18] Online Mendelian Inheritance in Man (OMIM) 308700 ANOS1
Lenz–Majewski hyperostotic dwarfism[18] Online Mendelian Inheritance in Man (OMIM) 151050 PTDSS1
Lissencephaly 3[18] Online Mendelian Inheritance in Man (OMIM) 611603 TUBA1A
Marden–Walker syndrome[6][18] Online Mendelian Inheritance in Man (OMIM) 248700 PIEZO2
MASA syndrome[18] Online Mendelian Inheritance in Man (OMIM) 303350 L1CAM
Microhydranencephaly[18] Online Mendelian Inheritance in Man (OMIM) 605013 NDE1
Mowat–Wilson syndrome[18] Online Mendelian Inheritance in Man (OMIM) 235730 ZEB2
NDH syndrome[18] Online Mendelian Inheritance in Man (OMIM) 610199 GLIS3
Oculoauriculofrontonasal syndrome[18] Online Mendelian Inheritance in Man (OMIM) 601452
Oculocerebrocutaneous syndrome[18] Online Mendelian Inheritance in Man (OMIM) 164180
Oculodentodigital dysplasia[18] Online Mendelian Inheritance in Man (OMIM) 164200 GJA1
Optiz–Kaveggia syndrome[18] Online Mendelian Inheritance in Man (OMIM) 305450 MED12
Otopalatodigital syndrome 2[18] Online Mendelian Inheritance in Man (OMIM) 304120 FLNA
Periventricular heterotopia X‐linked[18] Online Mendelian Inheritance in Man (OMIM) 300049 FLNA
Perlman syndrome[18] Online Mendelian Inheritance in Man (OMIM) 267000 DIS3L2
Pitt–Hopkins syndrome[18] Online Mendelian Inheritance in Man (OMIM) 610954 TCF4
Polycystic liver disease[6] Online Mendelian Inheritance in Man (OMIM) 174050
Proteus syndrome[18] Online Mendelian Inheritance in Man (OMIM) 176920 AKT1
Pseudotrisomy 13[18] Online Mendelian Inheritance in Man (OMIM) 264480
Retinal cone dystrophy 1[18] Online Mendelian Inheritance in Man (OMIM) 180020
Some forms of retinitis pigmentosa[6][25][18] Online Mendelian Inheritance in Man (OMIM) 268000
Robinow syndrome[18] Online Mendelian Inheritance in Man (OMIM) 268310 ROR2
Rubinstein–Taybi syndrome[18] Online Mendelian Inheritance in Man (OMIM) 180849 CREBBP
Sakoda complex[18] Online Mendelian Inheritance in Man (OMIM) 610871
Schinzel–Giedion syndrome[18] Online Mendelian Inheritance in Man (OMIM) 269150 SETBP1
Split-hand/foot malformation 3[18] Online Mendelian Inheritance in Man (OMIM) 246560
Spondyloepiphyseal dysplasia congenita[18] Online Mendelian Inheritance in Man (OMIM) 183900 COL2A1
Thanatophoric dysplasia[18] Online Mendelian Inheritance in Man (OMIM) 187600 FGFR3
Townes–Brocks syndrome[18] Online Mendelian Inheritance in Man (OMIM) 107480 SALL1, DACT1
Tuberous sclerosis[18] Online Mendelian Inheritance in Man (OMIM) 191100 TSC1, TSC2
VATER association[18] Online Mendelian Inheritance in Man (OMIM) 192350
Ven den Ende–Gupta syndrome[18] Online Mendelian Inheritance in Man (OMIM) 600920 SCARF2
Visceral heterotaxy[18] Online Mendelian Inheritance in Man (OMIM) 606325
Walker–Warburg syndrome[18] Online Mendelian Inheritance in Man (OMIM) 236670
Warburg Micro syndrome[18] Online Mendelian Inheritance in Man (OMIM) 615663 RAB3GAP1
X‐linked congenital hydrocephalus[18] Online Mendelian Inheritance in Man (OMIM) 307000 L1CAM
X‐linked lissencephaly[18] Online Mendelian Inheritance in Man (OMIM) 300067 DCX
Young–Simpson syndrome[18] Online Mendelian Inheritance in Man (OMIM) 603736 KAT6B

History

The discovery of cilia marked a pivotal moment in biological science. In the 1670s, Dutch microscopist Antonie van Leeuwenhoek described microscopic "animalcules" in rainwater, observing tiny, moving projections on their surfaces—structures that are now recognized as cilia. This was the first recorded observation of cellular appendages involved in locomotion and environmental sensing.[26]

Despite early recognition, the functional importance of cilia remained underappreciated for centuries. Non-motile, or primary cilia, were first described in 1898, but were largely dismissed as vestigial structures without biological significance.[3] It was not until the advent of advanced microscopy and molecular genetics in the late 20th and early 21st centuries that the essential roles of cilia in development and disease became clear.[3][26] Today, primary cilia are understood as sensory organelles that coordinate diverse signaling pathways such as Hedgehog and Wnt, and are critical for tissue patterning, cellular differentiation, and organ development.[1] Cilia function as cellular "antennae," detecting mechanical, chemical, and thermal cues from the environment.[3][26]

The modern era of ciliopathy research has been driven by advances in mammalian genetics. These have enabled the identification of mutations in cilia-related genes that underlie a wide spectrum of genetic disorders, now collectively referred to as ciliopathies. These include autosomal dominant and recessive polycystic kidney disease, nephronophthisis, Bardet–Biedl syndrome, Joubert syndrome, and others. The overlapping phenotypes of these diseases reflect the shared molecular architecture of cilia and their conserved roles across organ systems.[1] Foundational work in embryology by scientists such as Karl Ernst von Baer laid the conceptual groundwork for modern developmental biology. Although von Baer did not explicitly describe cilia, his meticulous observations of embryonic tissues likely included ciliated structures. His legacy continues to influence current research into the roles of cilia in early development, particularly in establishing left-right asymmetry and proper organ positioning.[1][26]

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 1.26 Chandra, Bharatendu; Tung, Moon Ley; Hsu, Ying; Scheetz, Todd; Sheffield, Val C. (Jul 2022). "Retinal ciliopathies through the lens of Bardet-Biedl Syndrome: Past, present and future" (in en). Progress in Retinal and Eye Research 89. doi:10.1016/j.preteyeres.2021.101035. PMID 34929400. https://linkinghub.elsevier.com/retrieve/pii/S1350946221000963. 
  2. ↑ Anvarian, Zeinab; Mykytyn, Kirk; Mukhopadhyay, Saikat; Pedersen, Lotte Bang; Christensen, Søren Tvorup (Apr 2019). "Cellular signalling by primary cilia in development, organ function and disease" (in en). Nature Reviews Nephrology 15 (4): 199–219. doi:10.1038/s41581-019-0116-9. ISSN 1759-5061. PMID 30733609. 
  3. ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 Braun, Daniela A.; Hildebrandt, Friedhelm (2017-03-01). "Ciliopathies". Cold Spring Harbor Perspectives in Biology 9 (3). doi:10.1101/cshperspect.a028191. ISSN 1943-0264. PMID 27793968. 
  4. ↑ 4.0 4.1 4.2 4.3 Chen, Holly Y.; Kelley, Ryan A.; Li, Tiansen; Swaroop, Anand (Feb 2021). "Primary cilia biogenesis and associated retinal ciliopathies" (in en). Seminars in Cell & Developmental Biology 110: 70–88. doi:10.1016/j.semcdb.2020.07.013. PMID 32747192. 
  5. ↑ Hyland, Rachael M.; Brody, Steven L. (2021-12-31). "Impact of Motile Ciliopathies on Human Development and Clinical Consequences in the Newborn". Cells 11 (1): 125. doi:10.3390/cells11010125. ISSN 2073-4409. PMID 35011687. 
  6. ↑ 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 6.13 6.14 6.15 6.16 6.17 6.18 6.19 6.20 6.21 6.22 6.23 6.24 6.25 6.26 6.27 6.28 "The ciliopathies: an emerging class of human genetic disorders". Annu Rev Genom Hum Genet 7: 125–48. 2006. doi:10.1146/annurev.genom.7.080505.115610. PMID 16722803. 
  7. ↑ Tan K, Liu P, Pang L, Yang W, Hou F (2018) A human ciliopathy with polycystic ovarian syndrome and multiple subcutaneous cysts: A rare case report. Medicine (Baltimore) 97(50)
  8. ↑ 8.0 8.1 8.2 8.3 8.4 Ross, Allison; PL Beales; J Hill (2008). "The Clinical, Molecular, and Functional Genetics of Bardet-Biedl Syndrome". Genetics of Obesity Syndromes. Oxford University Press. p. 177. ISBN 978-0-19-530016-1. https://books.google.com/books?id=SOvEYxO2V4AC. Retrieved 1 July 2009. 
  9. ↑ Yealland, G.; Jevtic, M.; Eckardt, K.-U.; Schueler, M. (2023). "Modeling ciliopathies in patient-derived primary cells". Cilia: From Mechanisms to Disease - Part B. Methods in Cell Biology. 176. pp. 139–158. doi:10.1016/bs.mcb.2023.02.016. ISBN 978-0-443-18588-5. https://pubmed.ncbi.nlm.nih.gov/37164535. 
  10. ↑ 10.0 10.1 10.2 Vrabič, N.; Fakin, A.; Tekavčič Pompe, M. (Oct 2024). "Spectrum and frequencies of extraocular features reported in CEP290-associated ciliopathy- a systematic review". Journal Français d'Ophtalmologie 47 (8). doi:10.1016/j.jfo.2024.104232. ISSN 1773-0597. PMID 39213781. 
  11. ↑ 11.0 11.1 11.2 Arora, Shashank; Rana, Mausam; Sachdev, Ananya; D'Souza, Jacinta S. (2023). "Appearing and disappearing acts of cilia". Journal of Biosciences 48 (1): 8. doi:10.1007/s12038-023-00326-6. ISSN 0973-7138. PMID 36924208. 
  12. ↑ Wallmeier, Julia; Nielsen, Kim G.; Kuehni, Claudia E.; Lucas, Jane S.; Leigh, Margaret W.; Zariwala, Maimoona A.; Omran, Heymut (2020-09-17). "Motile ciliopathies". Nature Reviews. Disease Primers 6 (1): 77. doi:10.1038/s41572-020-0209-6. ISSN 2056-676X. PMID 32943623. 
  13. ↑ Goetz, Sarah C.; Anderson, Kathryn V. (May 2010). "The primary cilium: a signalling centre during vertebrate development". Nature Reviews. Genetics 11 (5): 331–344. doi:10.1038/nrg2774. ISSN 1471-0064. PMID 20395968. 
  14. ↑ Focșa, Ina Ofelia; Budișteanu, Magdalena; Bălgrădean, Mihaela (Sep 2021). "Clinical and genetic heterogeneity of primary ciliopathies (Review)". International Journal of Molecular Medicine 48 (3): 176. doi:10.3892/ijmm.2021.5009. ISSN 1791-244X. PMID 34278440. 
  15. ↑ 15.0 15.1 Mill, Pleasantine; Christensen, Søren T.; Pedersen, Lotte B. (Sep 2023). "Primary cilia as dynamic and diverse signalling hubs in development and disease". Nature Reviews. Genetics 24 (7): 421–441. doi:10.1038/s41576-023-00587-9. ISSN 1471-0064. PMID 37072495. 
  16. ↑ 16.0 16.1 Adams, M.; Smith, U. M.; Logan, C. V.; Johnson, C. A. (2008). "Recent advances in the molecular pathology, cell biology and genetics of ciliopathies". Journal of Medical Genetics 45 (5): 257–267. doi:10.1136/jmg.2007.054999. PMID 18178628. 
  17. ↑ 17.00 17.01 17.02 17.03 17.04 17.05 17.06 17.07 17.08 17.09 17.10 17.11 17.12 17.13 17.14 17.15 17.16 17.17 17.18 17.19 17.20 17.21 17.22 17.23 17.24 17.25 17.26 17.27 17.28 17.29 17.30 17.31 17.32 17.33 17.34 17.35 17.36 17.37 17.38 17.39 17.40 17.41 17.42 17.43 17.44 17.45 17.46 17.47 17.48 17.49 17.50 17.51 17.52 17.53 17.54 17.55 17.56 17.57 17.58 17.59 17.60 17.61 17.62 17.63 17.64 17.65 17.66 17.67 17.68 17.69 17.70 17.71 17.72 17.73 17.74 17.75 17.76 17.77 17.78 17.79 17.80 Horani, Amjad; Ferkol, Thomas W. (Mar 2021). "Understanding Primary Ciliary Dyskinesia and Other Ciliopathies". The Journal of Pediatrics 230: 15–22.e1. doi:10.1016/j.jpeds.2020.11.040. ISSN 1097-6833. PMID 33242470. 
  18. ↑ 18.00 18.01 18.02 18.03 18.04 18.05 18.06 18.07 18.08 18.09 18.10 18.11 18.12 18.13 18.14 18.15 18.16 18.17 18.18 18.19 18.20 18.21 18.22 18.23 18.24 18.25 18.26 18.27 18.28 18.29 18.30 18.31 18.32 18.33 18.34 18.35 18.36 18.37 18.38 18.39 18.40 18.41 18.42 18.43 18.44 18.45 18.46 18.47 18.48 18.49 18.50 18.51 18.52 18.53 18.54 18.55 18.56 18.57 18.58 18.59 18.60 18.61 18.62 18.63 18.64 18.65 18.66 18.67 18.68 18.69 18.70 18.71 18.72 18.73 18.74 18.75 18.76 18.77 18.78 18.79 18.80 18.81 18.82 18.83 18.84 18.85 18.86 18.87 18.88 18.89 18.90 18.91 18.92 Baker, Kate; Beales, Philip L. (2009). "Making sense of cilia in disease: The human ciliopathies" (in en). American Journal of Medical Genetics Part C: Seminars in Medical Genetics 151C (4): 281–295. doi:10.1002/ajmg.c.30231. ISSN 1552-4876. PMID 19876933. 
  19. ↑ 19.0 19.1 19.2 19.3 19.4 Davenport, J. R. (2005). "An incredible decade for the primary cilium: A look at a once-forgotten organelle". AJP: Renal Physiology 289 (6): F1159–F1169. doi:10.1152/ajprenal.00118.2005. PMID 16275743. 
  20. ↑ Kyttälä, Mira (May 2006). "Identification of the Meckel Syndrome Gene (MKS1) Exposes a Novel Ciliopathy". http://www.ktl.fi/attachments/suomi/julkaisut/julkaisusarja_a/2006/2006a05.pdf. 
  21. ↑ Gunay-Aygun M (November 2009). "Liver and Kidney Disease in Ciliopathies". Am J Med Genet C Semin Med Genet 151C (4): 296–306. doi:10.1002/ajmg.c.30225. PMID 19876928. 
  22. ↑ Gene therapy rescues cilia defects and restores olfactory function in a mammalian ciliopathy model
  23. ↑ "From cilia to cyst". Nat. Genet. 34 (4): 355–6. August 2003. doi:10.1038/ng0803-355. PMID 12923538. 
  24. ↑ Delgado-Escueta AV (2007). "Advances in Genetics of Juvenile Myoclonic Epilepsies". Epilepsy Curr 7 (3): 61–7. doi:10.1111/j.1535-7511.2007.00171.x. PMID 17520076. 
  25. ↑ Khanna, H.; Davis, E. E.; Murga-Zamalloa, C. A.; Estrada-Cuzcano, A.; Lopez, I.; Den Hollander, A. I.; Zonneveld, M. N.; Othman, M. I. et al. (2009). "A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathies". Nature Genetics 41 (6): 739–745. doi:10.1038/ng.366. PMID 19430481. 
  26. ↑ 26.0 26.1 26.2 26.3 Modarage, K.; Malik, S. A.; Goggolidou, P. (January 2022). "Molecular Diagnostics of Ciliopathies and Insights Into Novel Developments in Diagnosing Rare Diseases". British Journal of Biomedical Science 79. doi:10.3389/bjbs.2021.10221. ISSN 2474-0896. PMID 35996505. 
Classification
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