Details of Disease

General Information of Disease (ID: DISOBC7V)

Disease Name Primary ciliary dyskinesia
Synonyms
bronchiectasis, chronic sinusitis and dextrocardia syndrome; ciliary dyskinesia primary; Primary ciliary dyskinesia and situs inversus; Dextrocardia-bronchiectasis-sinusitis syndrome; Siewert syndrome; ICS; Primary ciliary dyskinesia, Kartagener type; Dextrocardia bronchiectasis and sinusitis; Immotile cilia syndrome, Kartagener type; PCD; ciliary motility disorder; Kartagener syndrome; Kartagener's syndrome; immotile ciliary syndrome
Disease Class LA75: Lung structural developmental anomaly
Definition
A rare, genetically heterogeneous, primarily respiratory disorder characterized by chronic upper and lower respiratory tract disease. Approximately half of PCD patients have an organ laterality defect (situs inversus totalis or situs ambiguus/heterotaxy).|Editor note: we deliberately merge two MESHes here
Disease Hierarchy
DIS6SVEE: Syndromic disease
DISGGAGJ: Respiratory disease
DIS10G4I: Ciliopathy
DISOBC7V: Primary ciliary dyskinesia
ICD Code
ICD-11
ICD-11: LA75.Y
ICD-9
ICD-9: 759.3
Expand ICD-11
'LA75.Y
Expand ICD-9
759.3
Disease Identifiers
MONDO ID
MONDO_0016575
MESH ID
D002925
UMLS CUI
C0008780
MedGen ID
3467
HPO ID
HP:0012265
Orphanet ID
244
SNOMED CT ID
86204009

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)
This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)
Drug Name Drug ID Highest Status Drug Type REF
VX-371 DMSTHG1 Phase 2 NA [1]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)
This Disease Is Related to 60 DOT Molecule(s)
Gene Name DOT ID Evidence Level Mode of Inheritance REF
ZMYND10 OT30KEZZ Supportive Autosomal dominant [2]
CFAP57 OT0P6D3O Limited Autosomal recessive [6]
CFAP74 OTVW2BGR Limited Autosomal recessive [6]
AK7 OTASZDJN Disputed Autosomal recessive [6]
BRWD1 OTOSRVDC Disputed Autosomal recessive [6]
CFAP43 OT6R8UGG Disputed Unknown [6]
DNAH8 OTGES2OU Disputed Autosomal recessive [6]
MNS1 OT67F3JQ Disputed Autosomal recessive [6]
CCDC103 OTWGXYEF Supportive Autosomal dominant [7]
CCDC39 OTXRCVUD Supportive Autosomal dominant [8]
CCDC40 OTFHEUUN Supportive Autosomal dominant [8]
CCDC65 OTLK1420 Supportive Autosomal dominant [9]
CCNO OT68CH0B Supportive Autosomal dominant [10]
CFAP298 OTTDRT2N Supportive Autosomal dominant [9]
CFAP300 OTJWZZIO Supportive Autosomal dominant [11]
DNAAF1 OTYLQLHO Supportive Autosomal dominant [8]
DNAAF2 OTB8YEJ5 Supportive Autosomal dominant [8]
DNAAF3 OT3OHO0O Supportive Autosomal dominant [12]
DNAAF4 OTVDYBJE Supportive Autosomal dominant [13]
DNAAF5 OTN0CT52 Supportive Autosomal dominant [14]
DNAAF6 OT7AT26M Supportive Autosomal dominant [15]
DNAH1 OTDZ26FJ Supportive Autosomal dominant [16]
DNAH11 OT6IYFVV Supportive Autosomal dominant [8]
DNAH5 OTC21RUS Supportive Autosomal dominant [8]
DNAH9 OTI2QIZQ Supportive Autosomal dominant [17]
DNAI1 OTF6C65Q Supportive Autosomal dominant [8]
DNAI2 OTHK0PS4 Supportive Autosomal dominant [8]
DNAJB13 OT264P6X Supportive Autosomal dominant [18]
DNAL1 OTU5AWIS Supportive Autosomal dominant [8]
DRC1 OT7WLL0X Supportive Autosomal dominant [19]
FOXJ1 OT7LLBZ7 Supportive Autosomal dominant [20]
GAS2L2 OTV0H6MJ Supportive Autosomal dominant [21]
GAS8 OT8KT2AK Supportive Autosomal dominant [22]
HYDIN OTY88F5F Supportive Autosomal dominant [23]
LRRC56 OTDXNK54 Supportive Autosomal dominant [24]
MCIDAS OTK1JVAH Supportive Autosomal dominant [25]
NEK10 OTN0JAYL Supportive Autosomal dominant [26]
NME8 OT4RULP5 Supportive Autosomal dominant [8]
ODAD1 OT5N7P0Y Supportive Autosomal dominant [27]
ODAD2 OTTC397T Supportive Autosomal dominant [28]
ODAD3 OT30XE9U Supportive Autosomal dominant [29]
ODAD4 OTL9URMM Supportive Autosomal dominant [30]
OFD1 OTAZW5TK Supportive Autosomal dominant [3]
RPGR OTJ7O69I Supportive Autosomal dominant [3]
RSPH1 OT3MR73R Supportive Autosomal dominant [31]
RSPH3 OTDPCNYN Supportive Autosomal dominant [32]
RSPH4A OTNDPGEE Supportive Autosomal dominant [8]
RSPH9 OTRAK1LK Supportive Autosomal dominant [8]
SPAG1 OT29JZKW Supportive Autosomal dominant [33]
SPEF2 OTO04K1T Supportive Autosomal dominant [34]
STK36 OTDWQNKK Supportive Autosomal dominant [4]
TTC12 OTDB24YV Supportive Autosomal dominant [35]
CFAP221 OTUVNCVZ Moderate Autosomal recessive [6]
TTC14 OTMTYOPF moderate Genetic Variation [36]
IFT122 OTSK3OAD Strong Biomarker [37]
INPP5E OTJF2AZ9 Strong Biomarker [38]
KIFC1 OTNQDS00 Strong Biomarker [39]
MLN OTBZ5SE5 Strong Genetic Variation [40]
POLL OTZ24QGM Strong Biomarker [41]
RPGRIP1L OT6Z069I Definitive Biomarker [42]
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⏷ Show the Full List of 60 DOT(s)
This Disease Is Related to 3 DTT Molecule(s)
Gene Name DTT ID Evidence Level Mode of Inheritance REF
RPGR TTHBDA9 Supportive Autosomal dominant [3]
STK36 TTX5KEQ Supportive Autosomal dominant [4]
RPGR TTHBDA9 Strong CausalMutation [5]
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References

1 ClinicalTrials.gov (NCT02871778) Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia (CLEAN-PCD). U.S. National Institutes of Health.
2 Mutations in ZMYND10, a gene essential for proper axonemal assembly of inner and outer dynein arms in humans and flies, cause primary ciliary dyskinesia. Am J Hum Genet. 2013 Aug 8;93(2):346-56. doi: 10.1016/j.ajhg.2013.07.009. Epub 2013 Jul 25.
3 Clinical Practice Guidelines for Rare Diseases: The Orphanet Database. PLoS One. 2017 Jan 18;12(1):e0170365. doi: 10.1371/journal.pone.0170365. eCollection 2017.
4 Mutation of serine/threonine protein kinase 36 (STK36) causes primary ciliary dyskinesia with a central pair defect. Hum Mutat. 2017 Aug;38(8):964-969. doi: 10.1002/humu.23261. Epub 2017 Jun 15.
5 X-linked retinitis pigmentosa: mutation spectrum of the RPGR and RP2 genes and correlation with visual function. Invest Ophthalmol Vis Sci. 2000 Aug;41(9):2712-21.
6 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
7 CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms. Nat Genet. 2012 May 13;44(6):714-9. doi: 10.1038/ng.2277.
8 Primary Ciliary Dyskinesia. 2007 Jan 24 [updated 2019 Dec 5]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
9 Zebrafish Ciliopathy Screen Plus Human Mutational Analysis Identifies C21orf59 and CCDC65 Defects as Causing Primary Ciliary Dyskinesia. Am J Hum Genet. 2013 Oct 3;93(4):672-86. doi: 10.1016/j.ajhg.2013.08.015.
10 Mutations in CCNO result in congenital mucociliary clearance disorder with reduced generation of multiple motile cilia. Nat Genet. 2014 Jun;46(6):646-51. doi: 10.1038/ng.2961. Epub 2014 Apr 20.
11 C11orf70 Mutations Disrupting the Intraflagellar Transport-Dependent Assembly of Multiple Axonemal Dyneins Cause Primary Ciliary Dyskinesia. Am J Hum Genet. 2018 May 3;102(5):956-972. doi: 10.1016/j.ajhg.2018.03.024.
12 Mutations in axonemal dynein assembly factor DNAAF3 cause primary ciliary dyskinesia. Nat Genet. 2012 Mar 4;44(4):381-9, S1-2. doi: 10.1038/ng.1106.
13 DYX1C1 is required for axonemal dynein assembly and ciliary motility. Nat Genet. 2013 Sep;45(9):995-1003. doi: 10.1038/ng.2707. Epub 2013 Jul 21.
14 Whole-exome capture and sequencing identifies HEATR2 mutation as a cause of primary ciliary dyskinesia. Am J Hum Genet. 2012 Oct 5;91(4):685-93. doi: 10.1016/j.ajhg.2012.08.022.
15 Mutations in PIH1D3 Cause X-Linked Primary Ciliary Dyskinesia with Outer and Inner Dynein Arm Defects. Am J Hum Genet. 2017 Jan 5;100(1):160-168. doi: 10.1016/j.ajhg.2016.11.019. Epub 2016 Dec 29.
16 Variation in DNAH1 may contribute to primary ciliary dyskinesia. BMC Med Genet. 2015 Mar 17;16:14. doi: 10.1186/s12881-015-0162-5.
17 Mutations in Outer Dynein Arm Heavy Chain DNAH9 Cause Motile Cilia Defects and Situs Inversus. Am J Hum Genet. 2018 Dec 6;103(6):984-994. doi: 10.1016/j.ajhg.2018.10.016. Epub 2018 Nov 21.
18 Mutations in DNAJB13, Encoding an HSP40 Family Member, Cause Primary Ciliary Dyskinesia and Male Infertility. Am J Hum Genet. 2016 Aug 4;99(2):489-500. doi: 10.1016/j.ajhg.2016.06.022.
19 The nexin-dynein regulatory complex subunit DRC1 is essential for motile cilia function in algae and humans. Nat Genet. 2013 Mar;45(3):262-8. doi: 10.1038/ng.2533. Epub 2013 Jan 27.
20 De Novo Mutations in FOXJ1 Result in a Motile Ciliopathy with Hydrocephalus and Randomization of Left/Right Body Asymmetry. Am J Hum Genet. 2019 Nov 7;105(5):1030-1039. doi: 10.1016/j.ajhg.2019.09.022. Epub 2019 Oct 17.
21 A biallelic mutation links MYORG to autosomal-recessive primary familial brain calcification. Brain. 2019 Feb 1;142(2):e4. doi: 10.1093/brain/awy343.
22 Loss-of-Function GAS8 Mutations Cause Primary Ciliary Dyskinesia and Disrupt the Nexin-Dynein Regulatory Complex. Am J Hum Genet. 2015 Oct 1;97(4):546-54. doi: 10.1016/j.ajhg.2015.08.012. Epub 2015 Sep 17.
23 Recessive HYDIN mutations cause primary ciliary dyskinesia without randomization of left-right body asymmetry. Am J Hum Genet. 2012 Oct 5;91(4):672-84. doi: 10.1016/j.ajhg.2012.08.016. Epub 2012 Sep 27.
24 Biallelic Mutations in LRRC56, Encoding a Protein Associated with Intraflagellar Transport, Cause Mucociliary Clearance and Laterality Defects. Am J Hum Genet. 2018 Nov 1;103(5):727-739. doi: 10.1016/j.ajhg.2018.10.003.
25 MCIDAS mutations result in a mucociliary clearance disorder with reduced generation of multiple motile cilia. Nat Commun. 2014 Jul 22;5:4418. doi: 10.1038/ncomms5418.
26 A human ciliopathy reveals essential functions for NEK10 in airway mucociliary clearance. Nat Med. 2020 Feb;26(2):244-251. doi: 10.1038/s41591-019-0730-x. Epub 2020 Jan 20.
27 Splice-site mutations in the axonemal outer dynein arm docking complex gene CCDC114 cause primary ciliary dyskinesia. Am J Hum Genet. 2013 Jan 10;92(1):88-98. doi: 10.1016/j.ajhg.2012.11.002. Epub 2012 Dec 20.
28 ARMC4 mutations cause primary ciliary dyskinesia with randomization of left/right body asymmetry. Am J Hum Genet. 2013 Aug 8;93(2):357-67. doi: 10.1016/j.ajhg.2013.06.009. Epub 2013 Jul 11.
29 CCDC151 mutations cause primary ciliary dyskinesia by disruption of the outer dynein arm docking complex formation. Am J Hum Genet. 2014 Sep 4;95(3):257-74. doi: 10.1016/j.ajhg.2014.08.005.
30 TTC25 Deficiency Results in Defects of the Outer Dynein Arm Docking Machinery and Primary Ciliary Dyskinesia with Left-Right Body Asymmetry Randomization. Am J Hum Genet. 2016 Aug 4;99(2):460-9. doi: 10.1016/j.ajhg.2016.06.014.
31 Loss-of-function mutations in RSPH1 cause primary ciliary dyskinesia with central-complex and radial-spoke defects. Am J Hum Genet. 2013 Sep 5;93(3):561-70. doi: 10.1016/j.ajhg.2013.07.013. Epub 2013 Aug 29.
32 RSPH3 Mutations Cause Primary Ciliary Dyskinesia with Central-Complex Defects and a Near Absence of Radial Spokes. Am J Hum Genet. 2015 Jul 2;97(1):153-62. doi: 10.1016/j.ajhg.2015.05.004. Epub 2015 Jun 11.
33 Mutations in SPAG1 cause primary ciliary dyskinesia associated with defective outer and inner dynein arms. Am J Hum Genet. 2013 Oct 3;93(4):711-20. doi: 10.1016/j.ajhg.2013.07.025. Epub 2013 Sep 19.
34 SPEF2- and HYDIN-Mutant Cilia Lack the Central Pair-associated Protein SPEF2, Aiding Primary Ciliary Dyskinesia Diagnostics. Am J Respir Cell Mol Biol. 2020 Mar;62(3):382-396. doi: 10.1165/rcmb.2019-0086OC.
35 Loss of UGP2 in brain leads to a severe epileptic encephalopathy, emphasizing that bi-allelic isoform-specific start-loss mutations of essential genes can cause genetic diseases. Acta Neuropathol. 2020 Mar;139(3):415-442. doi: 10.1007/s00401-019-02109-6. Epub 2019 Dec 9.
36 Mutations in CCDC39 and CCDC40 are the major cause of primary ciliary dyskinesia with axonemal disorganization and absent inner dynein arms.Hum Mutat. 2013 Mar;34(3):462-72. doi: 10.1002/humu.22261. Epub 2013 Feb 11.
37 Cranioectodermal Dysplasia, Sensenbrenner syndrome, is a ciliopathy caused by mutations in the IFT122 gene. Am J Hum Genet. 2010 Jun 11;86(6):949-56. doi: 10.1016/j.ajhg.2010.04.012. Epub 2010 May 20.
38 INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse. Nat Genet. 2009 Sep;41(9):1027-31. doi: 10.1038/ng.427. Epub 2009 Aug 9.
39 Genomic organization of the HSET locus and the possible association of HLA-linked genes with immotile cilia syndrome (ICS).Immunogenetics. 1999 Jul;49(7-8):644-52. doi: 10.1007/s002510050660.
40 The motilin gene: subregional localisation, tissue expression, DNA polymorphisms and exclusion as a candidate gene for the HLA-associated immotile cilia syndrome.Hum Genet. 1994 Dec;94(6):671-4. doi: 10.1007/BF00206962.
41 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 Apr;22(8):2769-76. doi: 10.1128/MCB.22.8.2769-2776.2002.
42 The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome. Nat Genet. 2007 Jul;39(7):875-81. doi: 10.1038/ng2039. Epub 2007 Jun 10.