Genetic defects in ciliary structure and function

Annual Review of Physiology

Volumn 69, Issue , 2007, Pages 423-450

  Zariwala, Maimoona A ^a   Knowles, Michael R ^a   Omran, Heymut ^b  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF FREIBURG   (Germany)

Author keywords

Dynein; Kartagener syndrome; Primary ciliary dyskinesia (pcd); Situs inversus

Indexed keywords

DYNEIN ADENOSINE TRIPHOSPHATASE; NITRIC OXIDE;

AUTOSOMAL RECESSIVE DISORDER; AXONEME; CELL MEMBRANE; CELL ULTRASTRUCTURE; CILIARY DYSKINESIA; CILIARY MOTILITY; CILIATED EPITHELIUM; DNAH5 GENE; DNAI1 GENE; DYSOSTOSIS; EUKARYOTIC FLAGELLUM; GENE; GENE MUTATION; GENETIC ANALYSIS; HUMAN; IMMUNOFLUORESCENCE; KARTAGENER SYNDROME; MALE INFERTILITY; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN LOCALIZATION; RETINITIS PIGMENTOSA; REVIEW; SITUS INVERSUS;

ANIMALS; CILIA; CILIARY MOTILITY DISORDERS; DNA; DYNEIN ATPASE; FLAGELLA; HUMANS;

EID: 33947525850     PISSN: 00664278     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.physiol.69.040705.141301     Document Type: Review

References (129)

1. Ibanez-Tallon I, Heintz N, Omran H. 2003. To beat or not to beat: roles of cilia in development and disease. Hum. Mol. Genet. 12:R27-35
2. Noone PG, Zariwala M, Knowles MR. 2006. Primary ciliary dyskinesia. In Principles of Molecular Medicine, ed. MS Runge, C Patterson, pp. 239-50. Totowa, New Jersey: Humana Press
3. Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, et al. 2003. Polycystics 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat. Genet. 33:129-37
4. Hildebrandt F, Otto E. 2005. Cilia and centrosomes: a unifying pathogenic concept for cystic kidney disease? Nat. Rev. Genet. 6:928-40
5. Badano JL, Mitsuma N, Beales PL, Katsanis N. 2006. The ciliopathies: an emerging class of human genetic disorders. Annu. Rev. Genomics Hum. Genet. 7:125-48
6. Besharse JC, Horst CJ. 1990. The photoreceptor connecting cilium. A model for the transition zone. In Ciliary and Flagellar Membranes, ed. RA Bloodgood, pp. 389-417. New York: Plenum Publ. Corp.
7. Marszalek JR, Liu X, Roberts EA, Chui D, Marth JD, et al. 2000. Genetic evidence for selective transport of opsin and arrestin by kinesin-II in mammalian photoreceptors. Cell 102:175-87
8. Pazour GJ, Baker SA, Deane JA, Cole DG, Diekert BL, Rosenbaum JL, Witman GB, Besharse JC. 2002. The intraflagellar transport protein, IFT88, is essential for vertebrate photoreceptor assembly and maintenance. J. Cell Biol. 157:103-13
9. Moore SJ, Green JS, Fan Y, Bhogal AK, Dicks E, et al. 2005. Clinical and genetic epidemiology of Bardet-Biedl syndrome in Newfoundland: a 22-year prospective, population-based, cohort study. Am. J. Med. Genet. A 132:352-60
10. Marshall JD, Bronson RT, Collin GB, Nordstrom AD, Maffei P, et al. 2005. New Alstrom syndrome phenotypes based on the evaluation of 182 cases. Arch. Intern. Med. 165:675-83
11. Praetorius HA, Spring KR. 2005. A physiological view of the primary cilium. Annu. Rev. Physiol. 67:515-29
12. Afzelius BA. 1976. A human syndrome caused by immotile cilia. Science 193:317-19
13. van's Gravesande KS, Omran H. 2005. Primary ciliary dyskinesia: clinical presentation, diagnosis and genetics. Ann. Med. 37:439-49
14. Narayan D, Krishnan SN, Upender M, Ravikumar TS, Mahoney MJ, et al. 1994. Unusual inheritance of primary ciliary dyskinesia (Kartagener's syndrome). J. Med. Genet. 31:493-96
15. Dry KL, Manson FD, Lennon A, Bergen AA, van Dorp DB, Wright AF. 1999. Identification of a 5′ splice site mutation in the RPGR gene in a family with X-linked retinitis pigmentosa (RP3). Hum. Mutat. 13:141-45
16. Iannaccone A, Breuer DK, Wang XF, Kuo SF, Normando EM, et al. 2003. Clinical and immunohistochemical evidence for an X-linked retinitis pigmentosa syndrome with recurrent infections and hearing loss in association with an RPGR mutation. J. Med. Genet. 40:e118
17. van Dorp DB, Wright AF, Carothers AD, Bleeker-Wagemakers EM. 1992. A family with RP3 type of X-linked retinitis pigmentosa: an association with ciliary abnormalities. Hum. Genet. 88:331-34
18. Zito I, Downes SM, Patel RJ, Cheetham ME, Ebenezer ND, et al. 2003. RPGR mutation associated with retinitis pigmentosa, impaired hearing, and sinorespiratory infections. J. Med. Genet. 40:609-15
19. Moore A, Escudier E, Roger G, Tamalet A, Pelosse B, et al. 2006. RPGR is mutated in patients with a complex X-linked phenotype combining primary ciliary dyskinesia and retinitis pigmentosa. J. Med. Genet. 43:326-33
20. Krawczynski MR, Witt M. 2004. PCD and RP: X-linked inheritance of both disorders? Pediatr. Pulmonol. 38:88-89
21. Budny B, Chen W, Omran H, Fliegauf M, Tzschach A, et al. 2006. A novel X-linked recessive mental retardation syndrome comprising macrocephaly and ciliary dysfunction is allelic to oral-facial-digital type I syndrome. Hum. Genet. 120:171-78
22. Afzelius BA, Mossberg B, Bergstrom SE. 2001. Immotile cilia syndrome (primary ciliary dyskinesia), including Kartagener syndrome. In The Metabolic and Molecular Basis of Inherited Disease, ed. CR Scriver, AL Beaudet, WS Sly, D Valle, B Childs, et al., pp. 4817-27. New York: McGraw-Hill
23. El Zein L, Omran FI, Bouvagnet P. 2003. Lateralization defects and ciliary dyskinesia: lessons from algae. Trends Genet. 19:162-67
24. Rott HD. 1979. Kartagener's syndrome and the syndrome of immotile cilia. Hum. Genet. 46:249-61
25. Nonaka S, Tanaka Y, Okada Y, Takeda S, Harada A, et al. 1998. Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein. Cell 95:829-37
26. Kennedy MP, Leigh MW, Dell S, Morgan L, Molina PL, et al. 2006. Primary ciliary dyskinesia and situs ambiguus/heterotaxy: organ laterality defects other than situs inversus totalis. Proc. Am. Thorac. Soc. 3:A399 (Abstr.)
27. Afzelius BA, Eliasson R. 1983. Male and female infertility problems in the immotile-cilia syndrome. Eur. J. Respir. Dis. Suppl. 127:144-47
28. Munro NC, Currie DC, Lindsay KS, Ryder TA, Rutman A, et al. 1994. Fertility in men with primary ciliary dyskinesia presenting with respiratory infection. Thorax 49:684-87
29. Kennedy MP, Noone PG, Carson J, Molina PL, Ghio A, et al. 2006. Calcium stone lithoptysis in primary ciliary dyskinesia. Respir. Med. 101:76-83
30. Coren ME, Meeks M, Morrison I, Buchdahl RM, Bush A. 2002. Primary ciliary dyskinesia: age at diagnosis and symptom history. Acta Paediatr. 91:667-69
31. Luck DJ. 1984. Genetic and biochemical dissection of the eucaryotic flagellum. J. Cell Biol. 98:789-94
32. 31a. Satir P, Christensen ST. 2007. Overview of structure and function of mammalian cilia. Annu. Rev. Physiol. 69:377-400
33. 31b. Salathe M. 2007. Regulation of mammalian ciliary function. Annu. Rev. Physiol 69:401-22
34. 31c. DiBella LM, King SM. 2001. Dynein motor of the Chlamydomonas flagellum. Int. Rev. Cytol. 210:227-68
35. Pazour GJ, Agrin N, Walker BL, Witman GB. 2006. Identification of predicted human outer dynein arm genes - candidates for primary ciliary dyskinesia genes. J. Med. Genet. 43:62-73
36. Hastie AT, Dicker DT, Hingley ST, Kueppers F, Fliggins ML, Weinbaum G. 1986. Isolation of cilia from porcine tracheal epithelium and extraction of dynein arms. Cell Motil. Cytoskel. 6:25-34
37. Witman GB, Wilkerson CG, King SM. 1994. The biochemistry, genetics, and molecular biology of flagellar dynein. In Microtubules, ed. J Hyams, C Lloyd, pp. 229-49. New York: Wiley-Liss
38. King SM, Gatti JL, Moss AG, Witman GB. 1990. Outer-arm dynein from trout spermatozoa: substructural organization. Cell Motil. Cytoskel. 16:266-78
39. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. 1990. Basic local alignment search tool. J. Mol. Biol. 215:403-10
40. Olbrich H, Haffner K, Kispert A, Volkel A, Volz A, et al. 2002. Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left-right asymmetry. Nat. Genet. 30:43-44
41. Kispert A, Petty M, Olbrich LI, Volz A, Ketelsen UP, et al. 2003. Genotype-phenotype correlations in PCD patients carrying DNAH5 mutations. Thorax 58:552-54
42. Ibanez-Tallon I, Pagenstecher A, Fliegauf M, Olbrich H, Kispert A, et al. 2004. Dysfunction of axonemal dynein heavy chain Mdnah5 inhibits ependymal flow and reveals a novel mechanism for hydrocephalus formation. Hum. Mol. Genet. 13:2133-41
43. Reed W, Carson JL, Moats-Staats BM, Lucier T, Liu P, et al. 2000. Characterization of an axonemal dynein heavy chain expressed early in airway epithelial ciliogenesis. Am. J. Respir. Cell Mol. Biol. 23:734-41
44. Chapelin C, Duriez B, Magnino F, Goossens M, Escudier E, Amselem S. 1997. Isolation of several human axonemal dynein heavy chain genes: genomic structure of the catalytic site, phylogenetic analysis and chromosomal assignment. FEBS Lett. 412:325-30
45. Supp DM, Witte DP, Potter SS, Brueckner M. 1997. Mutation of an axonemal dynein affects left-right asymmetry in inversus viscerum mice. Nature 389:963-96
46. Fliegauf M, Olbrich LI, Horvath J, Wildhaber JH, Zariwala MA, et al. 2005. Mislocalization of DNAH5 and DNAH9 in respiratory cells from patients with primary ciliary dyskinesia. Am. J. Respir. Crit. Care Med. 171:1343-49
47. Porter ME, Sale WS. 2000. The 9 + 2 axoneme anchors multiple inner arm dyneins and a network of kinases and phosphatases that control motility. J. Cell Biol. 15LF37-42
48. Nicastro D, Schwartz C, Pierson J, Gaudette R, Porter ME, McIntosh JR. 2006. The molecular architecture of axonemes revealed by cryoelectron tomography. Science 313:944-48
49. Carson JL, Collier AM, Hu S-CS. 1985. Acquired ciliary defects in nasal epithelium of children with acute viral upper respiratory infections. N. Engl. J. Med. 312:463-68
50. Olbrich H, Horvath J, Fekete A, Loges NT, van's Gravesande KS, Blum A, Hormann K, Omran H. 2006. Axonemal localization of the dynein component DNAH5 is not altered in secondary ciliary dyskinesia. Pediatr. Res. 59:418-22
51. Escudier E, Couprie M, Duriez B, Roudot-Thoraval F, Millepied MC, et al. 2002. Computer-assisted analysis helps detect inner dynein arm abnormalities. Am. J. Respir. Crit. Care Med. 166:1257-62
52. Bush A, Ferkol T. 2006. Movement: the emerging genetics of primary ciliary dyskinesia. Am. J. Respir. Crit. Care Med. 174:109-10
53. Carda C, Armengot M, Escribano A, Peydro A. 2005. Ultrastructural patterns of primary ciliary dyskinesia syndrome. Ultrastruct. Pathol. 29:3-8
54. Carlen B, Stenram U. 2005. Primary ciliary dyskinesia: a review. Ultrastruct. Pathol. 29:217-20
55. Noone PG, Leigh MW, Sannuti A, Minnix SL, Carson JL, et al. 2004. Primary ciliary dyskinesia: diagnostic and phenotypic features. Am. J. Respir. Crit. Care Med. 169:459-67
56. Chilvers MA, Rutman A, O'Callaghan C. 2003. Ciliary beat pattern is associated with specific ultrastructural defects in primary ciliary dyskinesia. J. Allergy Clin. Immunol. 112:518-24
57. Jorissen M, Willems T, Van der SB, Verbeken E, De Boeck K. 2000. Ultrastructural expression of primary ciliary dyskinesia after ciliogenesis in culture. Acta Otorhinolaryngol. Belg. 54:343-56
58. Omran H, Haffner K, Volkel A, Kuehr J, Ketelsen UP, et al. 2000. 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. 23:696-702
59. Wilkerson CG, King SM, Witman GB. 1994. Molecular analysis of the gamma heavy chain of Chlamydomonas flagellar outer-arm dynein. J. Cell Sci. 107(Pt. 3):497-506
60. Hornef N, Olbrich H, Horvath J, Zariwala MA, Fliegauf M, et al. 2006. DNAH5 mutations are a common cause of primary ciliary dyskinesia with outer dynein arm defects. Am. J. Respir. Crit. Care Med. 174:120-26
61. Rosenbaum JL, Witman GB. 2002. Intraflagellar transport. Nat. Rev. Mol. Cell Biol. 3:813-25
62. Avidor-Reiss T, Maer AM, Koundakjian E, Polyanovsky A, Keil T, et al. 2004. Decoding cilia function: defining specialized genes required for compartmentalized cilia biogenesis. Cell 117:527-39
63. Han YG, Kwok BH, Kernan MJ. 2003. Intraflagellar transport is required in Drosophila to differentiate sensory cilia but not sperm. Curr. Biol. 13:1679-86
64. Pennarun G, Escudier E, Chapelin C, Bridoux AM, Cacheux V, et al. 1999. Loss-of-function mutations in a human gene related to Chlamydomonas reinhardtii dynein IC78 result in primary ciliary dyskinesia. Am. J. Hum. Genet. 65:1508-19
65. Guichard C, Harricane MC, Lafitte JJ, Godard P, Zaegel M, et al. 2001. Axonemal dynein intermediate-chain gene (DNAI1) mutations result in situs inversus and primary ciliary dyskinesia (Kartagener syndrome). Am. J. Hum. Genet. 68:1030-35
66. Zariwala M, Noone PG, Sannuti A, Minnix S, Zhou Z, et al. 2001. Germline mutations in an intermediate chain dynein cause primary ciliary dyskinesia. Am. J. Respir. Cell Mol. Biol. 25:577-83
67. Zariwala MA, Leigh MW, Ceppa F, Kennedy MP, Noone PG, et al. 2006. Mutations of DNAI1 in primary ciliary dyskinesia: evidence of founder effect in a common mutation. Am. J. Respir. Crit. Care Med. 174:858-66
68. Mitchell DR, Kang Y. 1991. Identification of oda6 as a Chlamydomonas dynein mutant by rescue with the wild-type gene. J. Cell Biol. 113:835-42
69. Bartoloni L, Blouin JL, Pan Y, Gehrig C, Maiti AK, et al. 2002. Mutations in the DNAH11 (axonemal heavy chain dynein type 11) gene cause one form of situs inversus totalis and most likely primary ciliary dyskinesia. Proc. Natl. Acad. Sci. USA 99:10282-86
70. Pagon RA, Daiger SP. 2004. Retinitis pigmentosa overview. http://www.geneclinics.org/
71. Hong DH, Pawlyk BS, Adamian M, Sandberg MA, Li T. 2005. A single, abbreviated RPGR-ORF15 variant reconstitutes RPGR function in vivo. Invest. Ophthalmol. Vis. Sci. 46:435-41
72. Hong DH, Pawlyk B, Sokolov M, Strissel KJ, Yang J, et al. 2003. RPGR isoforms in photoreceptor connecting cilia and the transitional zone of motile cilia. Invest. Ophthalmol. Vis. Sci. 44:2413-21
73. Hong DH, Pawlyk BS, Shang J, Sandberg MA, Berson EL, Li T. 2000. A retinitis pigmentosa GTPase regulator (RPGR)-deficient mouse model for X-linked retinitis pigmentosa (RP3). Proc. Natl. Acad. Sci USA 97:3649-54
74. Krawczynski MR, Dmenska H, Witt M. 2004. Apparent X-linked primary ciliary dyskinesia associated with retinitis pigmentosa and a hearing loss. J. Appl. Genet. 45:107-10
75. Ferrante MI, Giorgio G, Feather SA, Bulfone A, Wright V, et al. 2001. Identification of the gene for oral-facial-digital type I syndrome. Am. J. Hum. Genet. 68: 569-76
76. Ferrante MI, Zullo A, Barra A, Bimonte S, Messaddeq N, et al. 2006. Oral-facial-digital type I protein is required for primary cilia formation and left-right axis specification. Nat. Genet. 38:112-17
77. Romio L, Fry AM, Winyard PJ, Malcolm S, Woolf AS, Feather SA. 2004. OFD1 is a centrosomal/basal body protein expressed during mesenchymal-epithelial transition in human nephrogenesis. J. Am. Soc. Nephrol. 15:2556-68
78. Fliegauf M, Omran LI. 2006. Novel tools to unravel molecular mechanisms in cilia-related disorders. Trends Genet. 22:241-45
79. Li JB, Gerdes JM, Haycraft CJ, Fan Y, Teslovich TM, et al. 2004. Comparative genomics identifies a flagellar and basal body proteome that includes the BBS5 human disease gene. Cell 117:541-52
80. Piperno G, Huang B, Luck DJ. 1977. Two-dimensional analysis of flagellar proteins from wild-type and paralyzed mutants of Chlamydomonas reinhardtii. Proc. Natl. Acad. Sci. USA 74:1600-4
81. Pazour GJ, Agrin N, Leszyk J, Witman GB. 2005. Proteomic analysis ofa eukaryotic cilium. J. Cell Biol. 170:103-13
82. Ostrowski LE, Blackburn K, Radde KM, Moyer MB, Schlatzer DM, et al. 2002. A proteomic analysis of human cilia: identification of novel components. Mol. Cell. Proteomics 1:451-65
83. Blouin JL, Meeks M, Radhakrishna U, Sainsbury A, Gehring C, et al. 2000. Primary ciliary dyskinesia: A genome-wide linkage analysis reveals extensive locus heterogeneity. Eur. J. Hum. Genet. 8:109-18
84. Meeks M, Walne A, Spiden S, Simpson H, Mussaffi-Georgy H, et al. 2000. A locus for primary ciliary dyskinesia maps to chromosome 19q. J. Med. Genet. 37:241-44
85. Jeganathan D, Chodhari R, Meeks M, Faeroe O, Smyth D, et al. 2004. 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. 41:233-40
86. Geremek M, Zietkiewicz E, Diehl SR, Alizadeh BZ, Wijmenga C, Witt M. 2006. Linkage analysis localises a Kartagener syndrome gene to a 3.5 cM region on chromosome 15q24-25. J. Med. Genet. 43:e1
87. Ibanez-Tallon I, Gorokhova S, Heintz N. 2002. Loss of function of axonemal dynein Mdnab5 causes primary ciliary dyskinesia and hydrocephalus. Hum. Mol. Genet. 11:715-21
88. Bruni JE, del Bigio MR, Cardoso ER, Persaud TV. 1988. Neuropathology of congenital hydrocephalus in the SUMS/NP mouse. Acta Neurochir. 92:118-22
89. Sapiro R, Kostetskii I, Olds-Clarke P, Gerton GL, Radice GL, Strauss III JF. 2002. Male infertility, impaired sperm motility, and hydrocephalus in mice deficient in sperm-associated antigen 6. Mol. Cell Biol. 22:6298-305
90. Torikata C, Kijimoto C, Koto M. 1991. Ultrastructure of respiratory cilia of WIC-Hyd male rats. An animal model for human immotile cilia syndrome. Am. J. Pathol. 138:341-47
91. Kobayashi Y, Watanabe M, Okada Y, Sawa H, Takai H, et al. 2002. 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. 22:2769-76
92. Zariwala M, O'Neal WK, Noone PG, Leigh MW, Knowles MR, Ostrowski LE. 2004. Investigation of the possible role ofa novel gene, DPCD, in primary ciliary dyskinesia. Am. J. Respir. Cell Mol. Biol. 30:428-34
93. Bertocci B, De Smet A, Berek C, Weill JC, Reynaud CA. 2003. Immunoglobulin kappa light chain gene rearrangement is impaired in mice deficient for DNA polymerase mu. Immunity 19:203-11
94. Supp DM, Brueckner M, Kuehn MR, Witte DP, Lowe LA, et al. 1999. Targeted deletion of the ATP binding domain of left-right dynein confirms its role in specifying development of left-right asymmetries. Development 126:5495-504
95. Tanaka H, Iguchi N, Toyama Y, Kitamura K, Takahashi T, et al. 2004. Mice deficient in the axonemal protein Tektin-t exhibit male infertility and immotile-cilium syndrome due to impaired inner arm dynein function. Mol. Cell Biol. 24:7958-64
96. Neesen J, Kirschner R, Ochs M, Schmiedl A, Habermann B, et al. 2001. Disruption of an inner arm dynein heavy chain gene results in asthenozoospermia and reduced ciliary beat frequency. Hum. Mol. Genet. 10:1117-28
97. Chen J, Knowles HJ, Hebert JL, Hackett BP. 1998. Mutation of the mouse hepatocyte nuclear factor/forkhead homologue 4 gene results in an absence of cilia and random left-right asymmetry. J. Clin. Invest. 102:1077-82
98. Zhang Z, Sapiro R, Kapfhamer D, Bucan M, Bray J, et al. 2002. A sperm-associated WD repeat protein orthologous to Chlamydomonas PF20 associates with Spag6, the mammalian orthologue of Chlamydomonas PF16. Mol. Cell Biol. 22:7993-8004
99. Zhang Z, Kostetskii I, Tang W, Haig-Ladewig L, Sapiro R, et al. 2006. Deficiency of SPAG16L causes male infertility associated with impaired sperm motility. Biol. Reprod. 74:751-59
100. Lundberg JO, Weitzberg E, Nordvall SL, Kuylenstierna R, Lundberg JM, Alving K. 1994. Primarily nasal origin of exhaled nitric oxide and absence in Kartagener's syndrome. Eur. Respir. J. 7:1501-4
101. Karadag B, James AJ, Gultekin E, Wilson NM, Bush A. 1999. Nasal and lower airway level of nitric oxide in children with primary ciliary dyskinesia. Eur. Respir. J. 13:1402-5
102. Nowinski A, Hawrylkjewicz I, Sulikowska-Rowinska A, Gorecka D. 2002. Primary ciliary dyskinesia: Kartagener's syndrome and fertile male. Pneumonol. Alergol. Pol. 70:312-17
103. Narang I, Ersu R, Wilson NM, Bush A. 2002. Nitric oxide in chronic airway inflammation in children: diagnostic use and pathophysiological significance. Thorax 57:586-89
104. Gaston B, Drazen JM, Loscalzo J, Stamler JS. 1994. The biology of nitrogen oxides in the airways. Am. J. Respir. Crit, Care Med. 149:538-51
105. Yates DH, Kharitonov SA, Thomas PS, Barnes PJ. 1996. Endogenous nitric oxide is decreased in asthmatic patients by an inhibitor of inducible nitric oxide synthase. Am. J. Respir. Crit. Care Med. 154:247-50
106. Xue C, Botkin SJ, Johns RA. 1996. Localization of endothelial NOS at the basal microtubule membrane in ciliated epithelium of rat lung. J. Histochem. Cytochem. 44:463-71
107. Razani B, Engelman JA, Wang XB, Schubert W, Zhang XL, et al. 2001. Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. J. Biol. Chem. 276:38121-38
108. Brown DE, Hazucha MJ, Minnix SL, Knowles MR, Leigh MW. 2005. Nasal nitric oxide measurement during tidal breathing maneuvers: application for PCD screening. Proc. Am. Thorac. Soc. 2:A185 (Abstr.)
109. Stannard W, Rutman A, Wallis C, O'Callaghan C. 2004. Central microtubular agenesis causing primary ciliary dyskinesia. Am. J. Respir. Crit Care Med. 169:634-37
110. Bush A. 2000. Primary ciliary dyskinesia. Acta Otorhinolaiyngol. Belg. 54:317-24
111. Sadek CM, Damdimopoulos AE, Pelto-Huikko M, Gustafsson JA, Spyrou G, Miranda-Vizuete A. 2001. Sptrx-2, a fusion protein composed of one thioredoxin and three tandemly repeated NDP-kinase domains is expressed in human testis germ cells. Genes Cells 6:1077-90
112. Martin R, Mogg AE, Heywood LA, Nitschke L, Burke JF. 1989. Aminoglycoside suppression at UAG, UAA and UGA codons in Escherichia coli and human tissue culture cells. Mol. Gen. Genet. 217:411-18
113. Bedwell DM, Kaenjak A, Benos DJ, Bebok Z, Bubien JK, et al. 1997. Suppression of a CFTR premature stop mutation in a bronchial epithelial cell line. Nat. Med. 3:1280-84
114. Howard M, Frizzell RA, Bedwell DM. 1996. Aminoglycoside antibiotics restore CFTR function by overcoming premature stop functions. Nat. Med. 2:467-69
115. Wilschanski M, Yahav Y, Yaacov Y, Blau H, Bentur L, et al. 2003. Gentamicin-induced correction of CFTR function in patients with cystic fibrosis and CFTR stop mutations. N. Engl. J. Med. 349:1433-41
116. Bartoloni L, Blouin JL, Maiti AK, Sainsbury A, Rossier C, et al. 2001. Axonemal beta heavy chain dynein DNAH9: cDNA sequence, genomic structure, and investigation of its role in primary ciliary dyskinesia. Genomics 72:21-33
117. Blouin JL, Albrecht C, Gehrig C, Duriaux-Sail G, Strauss JF III, et al. 2003. Primary ciliary dyskinesia/Kartagener syndrome: searching for genes in a highly heterogeneous disorder. Am. J. Hum. Genet. 73(Suppl. 5) (Abstr. No. 2440)
118. Bartoloni L, Mitchison H, Pazour GJ, Maiti AK, Meeks M, et al. 2000. No deleterious mutations were found in three genes (HFH4, LCS, IC2) on human chromosome 17q in patients with primary ciliary dyskinesia. Eur. J. Hum. Genet. 8:P484 (Abstr.)
119. Pennarun G, Bridoux AM, Escudier E, Dastot-Le Moal F, Cacheux V, et al. 2002. Isolation and expression of the human hPF20 gene orthologous to Chlamydmnonas PF20: evaluation as a candidate for axonemal defects of respiratory cilia and sperm flagella. Am. J. Respir. Cell Mol. Biol. 26:362-7'0
120. Horvath J, Fliegauf M, Olbrich H, Kispert A, King SM, et al. 2005. Identification and analysis of axonemal dynein light chain 1 in primary ciliary dyskinesia patients. Am. J. Respir. Cell Mol. Biol. 33:41-47
121. Gehrig C, Albrecht C, Duriaus Sail G, Rossier C, Scamuffa N, DeLozier-Blancet C, Antonarakis SE, Blouin JL. 2002. Primary ciliary dyskinesia: mutation analysis in dynein light chain genes mapping to chromosome 1 (HP28) and 22 (DNAL4). Presented at Eur. Hum. Genet. Conf., Strasbourg, P0305 (Abstr.)
122. Neesen J, Drenckhahn JD, Tiede S, Burfeind P, Grzmil M, et al. 2002. Identification of the human ortholog of the t-complex-encoded protein TCTE3 and evaluation as a candidate gene for primary ciliary dyskinesia. Cytogenet, Genome Res. 98:38-44
123. Blouin JL, Gehrig C, Armengot M, Rutishauser M, Jorissen M, et al. 2002. DNAH3: characterization of the sequence and mutation search in patients with Primaiy Ciliaiy Dyskinesia. Presented at Eur. Plum. Genet. Conf., Strasbourg, P0304 (Abstr.)
124. Zhang YJ, O'Neal WK, Randell SH, Blackburn K, Moyer MB, et al. 2002. Identification of dynein heavy chain 7 as an inner arm component of human cilia that is synthesized but not assembled in a case of primary ciliary dyskinesia. J. Biol. Chem. 277:17906-15
125. Pennarun G, Bridoux AM, Escudier E, Amselem S, Duriez B. 2001. The human HP28 and HFH4 genes: evaluation as candidate genes for primary ciliary dyskinesia. Am. J. Respir. Crit. Care Med. 163:A538 (Abstr.)
126. Maiti AK, Bartoloni L, Mitchison HM, Meeks M, Chung E, et al. 2000. No deleterious mutations in the FOXJ1 (alias HFH-4) gene in patients with primary ciliary dyskinesia (PCD). Cytogenet. Cell Genet. 90:119-22
127. Afzelius BA. 2004. Cilia-related diseases. J. Pathol. 204:470-77
128. Berdon WE, Willi U. 2004. Situs inversus, bronchiectasis, and sinusitis and its relation to immotile cilia: history of the diseases and their discoverers - Manes Kartagener and Bjorn Afzelius. Pediatr. Radiol. 34:38-42
129. Chodhari R, Mitchison HM, Meeks M. 2004. Cilia, primary ciliary dyskinesia and molecular genetics. Paediatr. Respir. Rev. 5:69-76