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Abnormal respiratory cilia in non-syndromic Leber congenital amaurosis with CEP290 mutations
  1. J F Papon1,2,3,4,5,
  2. I Perrault6,
  3. A Coste1,2,3,4,
  4. B Louis1,
  5. X Gérard7,
  6. S Hanein6,
  7. L Fares-Taie6,
  8. S Gerber6,
  9. S Defoort-Dhellemmes8,
  10. A M Vojtek9,
  11. J Kaplan6,
  12. J M Rozet6,
  13. E Escudier1,9,10,11
  1. 1INSERM, Unit U955, Creteil, France
  2. 2Universite Paris-Est Creteil Val de Marne, Faculte de Medecine, UMR_S955, Creteil, France
  3. 3AP-HP, Groupe Henri-Mondor–Albert Chenevier, service d'ORL et de Chirurgie Cervico-Faciale, Creteil, France
  4. 4Hopital intercommunal, service d'ORL et de Chirurgie Cervico-Faciale, Creteil, France
  5. 5INSERM, Unit U933 Paris, France
  6. 6Unité de Recherches en Génétique et Epigénétique des Maladies Métaboliques, Neurosensorielles et du Dévelopement, INSERM U781 and Université Paris Descartes, CHU Necker Enfants Malades, Paris, France
  7. 7Genethon Evry, France
  8. 8Service d'Ophtalmogie, CHRU Roger Salengro, Lille, France
  9. 9Hopital intercommunal, Service D'anatomo-Pathologie (Laboratoire De Microscopie Electronique), Creteil, France
  10. 10Universite Paris 6, Faculte de Medecine, Paris, France
  11. 11AP-HP, Hopital Armand-Trousseau, Service De Genetique Et D'embryologie Medicales, Paris, France
  1. Correspondence to Dr Jean-Michel Rozet, Hopital Necker-Enfants Malades, 149 rue de Sèvres, 75743 Paris Cedex 15, France; jean-michel.rozet{at}


Background Leber congenital amaurosis (LCA) is the earliest and most severe inherited retinal degeneration. Isolated forms of LCA frequently result from mutation of the CEP290 gene which is expressed in various ciliated tissues.

Methods Seven LCA patients with CEP290 mutations were investigated to study otorhinolaryngologic phenotype and respiratory cilia. Nasal biopsies and brushing were performed to study cilia ultrastructure using transmission electron microscopy and ciliary beating using high-speed videomicroscopy, respectively. CEP290 expression in normal nasal epithelium was studied using real-time RT-PCR.

Results When electron microscopy was feasible (5/7), high levels of respiratory cilia defects were detected. The main defects concerned dynein arms, central complex and/or peripheral microtubules. All patients had a rarefaction of ciliated cells and a variable proportion of short cilia. Frequent but moderate and heterogeneous clinical and ciliary beating abnormalities were found. CEP290 was highly expressed in the neural retina and nasal epithelial cells compared with other tissues.

Discussion These data provide the first clear demonstration of respiratory cilia ultrastructural defects in LCA patients with CEP290 mutations. The frequency of these findings in LCA patients along with the high expression of CEP290 in nasal epithelium suggest that CEP290 has an important role in the proper development of both the respiratory ciliary structures and the connecting cilia of photoreceptors. The presence of respiratory symptoms in patients could represent additional clinical criteria to direct CEP290 genotyping of patients affected with the genetically heterogeneous cone-rod dystrophy subtype of LCA.

  • LCA
  • CEP290
  • ciliopathies
  • axonemal ultrastructure
  • ciliary movement
  • diagnostics tests
  • clinical genetics
  • respiratory medicine

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  • J F Papon and I Perrault contributed equally to this work.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the APHP, Necker local ethics committee (DC-2008-512, Paris-Necker).

  • Provenance and peer review Not commissioned; externally peer reviewed.