Immunofluorescence analysis and diagnosis of primary ciliary dyskinesia with radial spoke defects

American Journal of Respiratory Cell and Molecular Biology

Volumn 53, Issue 4, 2015, Pages 563-573

  Frommer, Adrien ^a   Hjeij, Rim ^a   Loges, Niki T ^a   Edelbusch, Christine ^a   Jahnke, Charlotte ^a   Raidt, Johanna ^a   Werner, Claudius ^a   Wallmeier, Julia ^a   Große Onnebrink, Jörg ^a   Olbrich, Heike ^a   Cindrić, Sandra ^a   Jaspers, Martine ^b   Boon, Mieke ^b   Memari, Yasin ^c   Durbin, Richard ^c   Kolb Kokocinski, Anja ^c   Sauer, Sascha ^d   Marthin, June K ^e   Nielsen, Kim G ^e   Amirav, Israel ^f   Elias, Nael ^g   Kerem, Eitan ^h   Shoseyov, David ^h   Haeffner, Karsten ⁱ   Omran, Heymut ^a   more..

^a UNIVERSITY HOSPITAL MÜNSTER   (Germany)

^b UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^c WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^d MAX PLANCK INSTITUTE FOR MOLECULAR GENETICS   (Germany)

^e Rigshospitalet   (Denmark)

^f UNIVERSITY OF ALBERTA   (Canada)

^g Ilan University   (Israel)

^h HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

ⁱ UNIVERSITY OF FREIBURG   (Germany)

Author keywords

Cilia; Human radial spoke protein 1; Human radial spoke protein 4A; Human radial spoke protein 9; Primary ciliary dyskinesia

Indexed keywords

CORE PROTEIN; RSPH1 PROTEIN; RSPH4A PROTEIN; RSPH9 PROTEIN; UNCLASSIFIED DRUG; CYTOSKELETON PROTEIN; DNA BINDING PROTEIN; PROTEIN; RSPH1 PROTEIN, HUMAN; RSPH4A PROTEIN, HUMAN; RSPH9 PROTEIN, HUMAN;

ADOLESCENT; ADULT; ARTICLE; BRONCHITIS; CHILD; CHRONIC COUGH; CILIARY DYSKINESIA; CLINICAL ARTICLE; CONGENITAL DISORDER; FEMALE; GENE FREQUENCY; GENE MUTATION; GENETIC ANALYSIS; GENETIC DISORDER; HOMOZYGOTE; HUMAN; IMMUNOFLUORESCENCE MICROSCOPY; LOSS OF FUNCTION MUTATION; MALE; MISSENSE MUTATION; PRESCHOOL CHILD; RADIAL SPOKE DEFECT; RHINORRHEA; SCHOOL CHILD; SINUSITIS; TRANSMISSION ELECTRON MICROSCOPY; WHEEZING; YOUNG ADULT; FLUORESCENT ANTIBODY TECHNIQUE; GENETICS; KARTAGENER SYNDROME; METABOLISM; NUCLEOTIDE SEQUENCE; PROTEIN MULTIMERIZATION;

ADOLESCENT; ADULT; CHILD; CHILD, PRESCHOOL; CYTOSKELETAL PROTEINS; DNA MUTATIONAL ANALYSIS; DNA-BINDING PROTEINS; FEMALE; FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT; HUMANS; KARTAGENER SYNDROME; MALE; MUTATION, MISSENSE; PROTEIN MULTIMERIZATION; PROTEINS; YOUNG ADULT;

EID: 84937531931     PISSN: 10441549     EISSN: 15354989     Source Type: Journal    
DOI: 10.1165/rcmb.2014-0483OC     Document Type: Article

References (49)

1. Ibañez-Tallon I, Heintz N, Omran H. To beat or not to beat: roles of cilia in development and disease. Hum Mol Genet 2003;12:R27-R35.
2. Marthin JK, Petersen N, Skovgaard LT, Nielsen KG. Lung function in patients with primary ciliary dyskinesia: a cross-sectional and 3-decade longitudinal study. Am J Respir Crit Care Med 2010;181: 1262-1268.
3. Knowles MR, Daniels LA, Davis SD, Zariwala MA, Leigh MW. Primary ciliary dyskinesia: recent advances in diagnostics, genetics, and characterization of clinical disease. Am J Respir Crit Care Med 2013; 188:913-922.
4. Zariwala MA, Knowles MR, Omran H. Genetic defects in ciliary structure and function. Annu Rev Physiol 2007;69:423-450.
5. Kennedy MP, Omran H, Leigh MW, Dell S, Morgan L, Molina PL, Robinson BV, Minnix SL, Olbrich H, Severin T, et al. Congenital heart disease and other heterotaxic defects in a large cohort of patients with primary ciliary dyskinesia. Circulation 2007;115:2814-2821.
6. Kuehni CE, Frischer T, Strippoli MF, Maurer E, Bush A, Nielsen KG, Escribano A, Lucas JSA, Yiallouros P, Omran H, et al. Factors influencing age at diagnosis of primary ciliary dyskinesia in European children. Eur Respir J 2010;36:1248-1258.
7. Pazour GJ, Agrin N, Leszyk J, Witman GB. Proteomic analysis of a eukaryotic cilium. J Cell Biol 2005;170:103-113.
8. Becker-Heck A, Loges NT, Omran H. Dynein dysfuntion as a cause of primary ciliary dyskinesia and other ciliopathies. In: King SM, editor. Dyneins, 1st ed. Waltham, MA: Academic Press; 2011. pp. 602-627.
9. Olbrich H, Häffner K, Kispert A, Völkel A, Volz A, Sasmaz G, Reinhardt R, Hennig S, Lehrach H, Konietzko N, et al. Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left-right asymmetry. Nat Genet 2002;30:143-144.
10. Pennarun G, Escudier E, Chapelin C, Bridoux AM, Cacheux V, Roger G, Clément A, Goossens M, Amselem S, Duriez B. Loss-of-function mutations in a human gene related to Chlamydomonas reinhardtii dynein IC78 result in primary ciliary dyskinesia. Am J Hum Genet 1999;65:1508-1519.
11. Mazor M, Alkrinawi S, Chalifa-Caspi V, Manor E, Sheffield VC, Aviram M, Parvari R. Primary ciliary dyskinesia caused by homozygous mutation in DNAL1, encoding dynein light chain 1. Am J Hum Genet 2011;88:599-607.
12. Duriez B, Duquesnoy P, Escudier E, Bridoux A, Escalier D, Rayet I, Marcos E, Vojtek A, Bercher J, Amselem S. A common variant in combination with a nonsense mutation in a member of the thioredoxin family causes primary ciliary dyskinesia. Proc Natl Acad Sci USA 2007;104:3336-3341.
13. Loges NT, Olbrich H, Fenske L, Mussaffi H, Horvath J, Fliegauf M, Kuhl H, Baktai G, Peterffy E, Chodhari R, et al. DNAI2 mutations cause primary ciliary dyskinesia with defects in the outer dynein arm. Am J Hum Genet 2008;83:547-558.
14. Knowles MR, Leigh MW, Ostrowski LE, Huang L, Carson JL, Hazucha MJ, Yin W, Berg JS, Davis SD, Dell SD, et al. Exome sequencing identifies mutations in CCDC114 as a cause of primary ciliary dyskinesia. Am J Hum Genet 2013;92:99-106.
15. Onoufriadis A, Paff T, Antony D, Shoemark A, Micha D, Kuyt B, Schmidts M, Petridi S, Dankert-Roelse JE, Haarman EG, et al. Splice-site mutations in the axonemal outer dynein arm docking complex gene CCDC114 cause primary ciliary dyskinesia. Am J Hum Genet 2013;92:88-98.
16. Hjeij R, Lindstrand A, Francis R, Zariwala MA, Liu X, Li Y, Damerla R, Dougherty GW, Abouhamed M, Olbrich H, et al. ARMC4 mutations cause primary ciliary dyskinesia with randomization of left/right body asymmetry. Am J Hum Genet 2013;93:357-367.
17. Hjeij R, Onoufriadis A, Watson CM, Slagle CE, Klena NT, Dougherty GW, Kurkowiak M, Loges NT, Diggle CP, Morante NF, et al. CCDC151 mutations cause primary ciliary dyskinesia by dysruption of the outer dynein arm docking complex formation. Am J Hum Genet 2014;95:257-274.
18. Loges NT, Olbrich H, Becker-Heck A, Häffner K, Heer A, Reinhard C, Schmidts M, Kispert A, Zariwala MA, Leigh MW, et al. Deletions and point mutations of LRRC50 cause primary ciliary dyskinesia due to dynein arm defects. Am J Hum Genet 2009;85: 883-889.
19. Omran H, Kobayashi D, Olbrich H, Tsukahara T, Loges NT, Hagiwara H, Zhang Q, Leblond G, O'Toole E, Hara C, et al. Ktu/PF13 is required for cytoplasmic pre-assembly of axonemal dyneins. Nature 2008; 456:611-616.
20. Mitchison HM, Schmidts M, Loges NT, Freshour J, Dritsoula A, Hirst RA, O'Callaghan C, Blau H, Al Dabbagh M, Olbrich H, et al. Mutations in axonemal dynein assembly factor DNAAF3 cause primary ciliary dyskinesia. Nat Genet 2012;44:381-389, S1-S2.
21. Tarkar A, Loges NT, Slagle CE, Francis R, Dougherty GW, Tamayo JV, Shook B, Cantino M, Schwartz D, Jahnke C, et al. DYX1C1 is required for axonemal dynein assembly and ciliary motility. Nat Genet 2013;45:995-1003.
22. Panizzi JR, Becker-Heck A, Castleman VH, Al-Mutairi DA, Liu Y, Loges NT, Pathak N, Austin-Tse C, Sheridan E, Schmidts M, et al. CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms. Nat Genet 2012;44: 714-719.
23. Kott E, Duquesnoy P, Copin B, Legendre M, Dastot-Le Moal F, Montantin G, Jeanson L, Tamalet A, Papon J, Siffroi J, et al. Loss-offunction mutations in LRRC6, a gene essential for proper axonemal assembly of inner and outer dynein arms, cause primary ciliary dyskinesia. Am J Hum Genet 2012;91:958-964.
24. Zariwala MA, Gee HY, Kurkowiak M, Al-Mutairi DA, Leigh MW, Hurd TW, Hjeij R, Dell SD, Chaki M, Dougherty GW, et al. ZMYND10 is mutated in primary ciliary dyskinesia and interacts with LRRC6. Am J Hum Genet 2013;93:336-345.
25. Horani A, Druley TE, Zariwala MA, Patel AC, Levinson BT, Van Arendonk LG, Thornton KC, Giacalone JC, Albee AJ, Wilson KS, et al. Whole-exome capture and sequencing identifies HEATR2 mutation as a cause of primary ciliary dyskinesia. Am J Hum Genet 2012;91:685-693.
26. Knowles MR, Ostrowski LE, Loges NT, Hurd T, Leigh MW, Huang L, Wolf WE, Carson JL, Hazucha MJ, Yin W, et al. Mutations in SPAG1 cause primary ciliary dyskinesia associated with defective outer and inner dynein arms. Am J Hum Genet 2013;93:711-720.
27. Austin-Tse C, Halbritter J, Zariwala MA, Gilberti RM, Gee HY, Hellman N, Pathak N, Liu Y, Panizzi JR, Patel-King RS, et al. Zebrafish ciliopathy screen plus human mutational analysis identifies C21orf59 and CCDC65 defects as causing primary ciliary dyskinesia. Am J Hum Genet 2013;93:672-686.
28. Becker-Heck A, Zohn IE, Okabe N, Pollock A, Lenhart KB, Sullivan- Brown J, McSheene J, Loges NT, Olbrich H, Haeffner K, 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.
29. Merveille A, Davis EE, Becker-Heck A, Legendre M, Amirav I, Bataille G, Belmont J, Beydon N, Billen F, Clément A, et al. CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs. Nat Genet 2011; 43:72-78.
30. Wirschell M, Olbrich H, Werner C, Tritschler D, Bower R, Sale WS, Loges NT, Pennekamp P, Lindberg S, Stenram U, et al. The nexin-dynein regulatory complex subunit DRC1 is essential for motile cilia function in algae and humans. Nat Genet 2013;45: 262-268.
31. Pigino G, Ishikawa T. Axonemal radial spokes: 3D structure, function and assembly. BioArchitecture 2012;2:50-58.
32. Yang P, Diener DR, Yang C, Kohno T, Pazour GJ, Dienes JM, Agrin NS, King SM, Sale WS, Kamiya R, et al. Radial spoke proteins of Chlamydomonas flagella. J Cell Sci 2006;119:1165-1174.
33. Castleman VH, Romio L, Chodhari R, Hirst RA, de Castro SCP, Parker KA, Ybot-Gonzalez P, Emes RD, Wilson SW, Wallis C, et al. Mutations in radial spoke head protein genes RSPH9 and RSPH4A cause primary ciliary dyskinesia with central-microtubular-pair abnormalities. Am J Hum Genet 2009;84:197-209.
34. Zietkiewicz E, Bukowy-Bieryłło Z, Voelkel K, Klimek B, Dmenéska H, Pogorzelski A, Sulikowska-Rowinéska A, Rutkiewicz E, Witt M. Mutations in radial spoke head genes and ultrastructural cilia defects in East-European cohort of primary ciliary dyskinesia patients. PLoS One 2012;7:e33667.
35. Onoufriadis A, Shoemark A, Schmidts M, Patel M, Jimenez G, Liu H, Thomas B, Dixon M, Hirst RA, Rutman A, et al. Targeted NGS gene panel identifies mutations in RSPH1 causing primary ciliary dyskinesia and a common mechanism for ciliary central pair agenesis due to radial spoke defects. Hum Mol Genet 2014;23: 3362-3374.
36. Kott E, Legendre M, Copin B, Papon J, Dastot-Le Moal F, Montantin G, Duquesnoy P, Piterboth W, Amram D, Bassinet L, et al. Loss-offunction mutations in RSPH1 cause primary ciliary dyskinesia with central-complex and radial-spoke defects. Am J Hum Genet 2013; 93:561-570.
37. Knowles MR, Ostrowski LE, Leigh MW, Sears PR, Davis SD, Wolf WE, Hazucha MJ, Carson JL, Olivier KN, Sagel SD, et al. Mutations in RSPH1 cause primary ciliary dyskinesia with a unique clinical and ciliary phenotype. Am J Respir Crit Care Med 2014;189:707-717.
38. Olbrich H, Schmidts M, Werner C, Onoufriadis A, Loges NT, Raidt J, Banki NF, Shoemark A, Burgoyne T, Al Turki S, et al. Recessive HYDIN mutations cause primary ciliary dyskinesia without randomization of left-right body asymmetry. Am J Hum Genet 2012;91:672-684.
39. Omran H, Loges NT. Immunofluorescence staining of ciliated respiratory epithelial cells. Methods Cell Biol 2009;91:123-133.
40. Fliegauf M, Olbrich H, Horvath J, Wildhaber JH, Zariwala MA, Kennedy M, Knowles MR, Omran H. Mislocalization of DNAH5 and DNAH9 in respiratory cells from patients with primary ciliary dyskinesia. Am J Respir Crit Care Med 2005;171:1343-1349.
41. Raidt J, Wallmeier J, Hjeij R, Große Onnebrink J, Pennekamp P, Loges NT, Olbrich H, Häffner K, Dougherty GW, Omran H, et al. Ciliary beat pattern and frequency in genetic variants of primary ciliary dyskinesia. Eur Respir J 2014;44:1579-1588.
42. Leigh MW, Hazucha MJ, Chawla KK, Baker BR, Shapiro AJ, Brown DE, Lavange LM, Horton BJ, Qaqish B, Carson JL, et al. Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia. Ann Am Thorac Soc 2013;10:574-581.
43. Pigino G, Bui KH, Maheshwari A, Lupetti P, Diener D, Ishikawa T. Cryoelectron tomography of radial spokes in cilia and flagella. J Cell Biol 2011;195:673-687.
44. Diener DR, Yang P, Geimer S, Cole DG, Sale WS, Rosenbaum JL. Sequential assembly of flagellar radial spokes. Cytoskeleton (Hoboken) 2011;68:389-400.
45. Daniels ML, Leigh MW, Davis SD, Armstrong MC, Carson JL, Hazucha M, Dell SD, Eriksson M, Collins FS, Knowles MR, et al. Founder mutation in RSPH4A identified in patients of Hispanic descent with primary ciliary dyskinesia. Hum Mutat 2013;34:1352-1356.
46. Burgoyne T, Lewis A, Dewar A, Luther P, Hogg C, Shoemark A, Dixon M. Characterizing the ultrastructure of primary ciliary dyskinesia transposition defect using electron tomography. Cytoskeleton (Hoboken) 2014;71:294-301.
47. Smith EF, Yang P. The radial spokes and central apparatus: mechanochemical transducers that regulate flagellar motility. Cell Motil Cytoskeleton 2004;57:8-17.
48. Kohno T, Wakabayashi K, Diener DR, Rosenbaum JL, Kamiya R. Subunit interactions within the Chlamydomonas flagellar spokehead. Cytoskeleton (Hoboken) 2011;68:237-246.
49. Lin J, Yin W, Smith MC, Song K, Leigh MW, Zariwala MA, Knowles MR, Ostrowski LE, Nicastro D. Cryo-electron tomography reveals ciliary defects underlying human RSPH1 primary ciliary dyskinesia. Nat Commun 2014;5:5727.