Article Text

Download PDFPDF

Original research
Deep phenotyping, including quantitative ciliary beating parameters, and extensive genotyping in primary ciliary dyskinesia
  1. Sylvain Blanchon1,2,
  2. Marie Legendre3,
  3. Mathieu Bottier1,
  4. Aline Tamalet4,
  5. Guy Montantin3,
  6. Nathalie Collot3,
  7. Catherine Faucon5,
  8. Florence Dastot3,
  9. Bruno Copin3,
  10. Annick Clement3,4,
  11. Marcel Filoche3,
  12. André Coste6,
  13. Serge Amselem3,
  14. Estelle Escudier3,
  15. Jean-Francois Papon1,7,
  16. Bruno Louis1
  1. 1 Universite Paris-Est, Faculte de Médecine, INSERM (Institut National pour la Santé et la Recherche Médicale) UMR_S955, Equipe 13, CNRS (Centre National pour la Recherche Scientifique), ERL 7000, Creteil, France
  2. 2 Department Woman-Mother-Child, Service of Pediatrics, Pediatric Pulmonology Unit, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
  3. 3 Sorbonne Universite, Faculte de Medecine, INSERM UMR_S933, APHP (Assistance Publique – Hopitaux de Paris), Unité de génétique moléculaire, Hopital Armand-Trousseau, Paris, France
  4. 4 APHP, Hopital Armand-Trousseau, Unite de Pneumologie Pédiatrique, Centre National de Reference des Maladies Respiratoires Rares, Creteil, France
  5. 5 Centre Hospitalier Intercommunal de Creteil, Service d’Anatomopathologie, Laboratoire de Microscopie Electronique, Creteil, France
  6. 6 APHP, Groupe Hospitalier Henri Mondor-Albert Chenevier et Centre Hospitalier Intercommunal de Creteil, Service d’ORL et de Chirurgie Cervico-faciale, Creteil, France
  7. 7 Universite Paris-Sud, Faculte de Medecine, APHP, Hopital Bicetre, Service d’ORL et de Chirurgie Cervico-maxillo-faciale, Le Kremlin Bicetre, France
  1. Correspondence to Dr Sylvain Blanchon, Universite Paris-Est, Faculte de Médecine, INSERM (Institut National pour la Santé et la Recherche Médicale) UMR_S955, Equipe 13, CNRS (Centre National pour la Recherche Scientifique), Creteil ERL7000, France; sylvain.blanchon{at}


Background Primary ciliary dyskinesia (PCD) is a rare genetic disorder resulting in abnormal ciliary motility/structure, extremely heterogeneous at genetic and ultrastructural levels. We aimed, in light of extensive genotyping, to identify specific and quantitative ciliary beating anomalies, according to the ultrastructural phenotype.

Methods We prospectively included 75 patients with PCD exhibiting the main five ultrastructural phenotypes (n=15/group), screened all corresponding PCD genes and measured quantitative beating parameters by high-speed video-microscopy (HSV).

Results Sixty-eight (91%) patients carried biallelic mutations. Combined outer/inner dynein arms (ODA/IDA) defect induces total ciliary immotility, regardless of the gene involved. ODA defect induces a residual beating with dramatically low ciliary beat frequency (CBF) related to increased recovery stroke and pause durations, especially in case of DNAI1 mutations. IDA defect with microtubular disorganisation induces a low percentage of beating cilia with decreased beating angle and, in case of CCDC39 mutations, a relatively conserved mean CBF with a high maximal CBF. Central complex defect induces nearly normal beating parameters, regardless of the gene involved, and a gyrating motion in a minority of ciliated edges, especially in case of RSPH1 mutations. PCD with normal ultrastructure exhibits heterogeneous HSV values, but mostly an increased CBF with an extremely high maximal CBF.

Conclusion Quantitative HSV analysis in PCD objectives beating anomalies associated with specific ciliary ultrastructures and genotypes. It represents a promising approach to guide the molecular analyses towards the best candidate gene(s) to be analysed or to assess the pathogenicity of the numerous sequence variants identified by next-generation-sequencing.

  • primary ciliary dyskinesia
  • cilia
  • video-microscopy
  • electron microscopy
  • genotype
View Full Text

Statistics from


  • Contributors Conception and design of the study: SB, ML, EE, JFP, BL. Acquisition, analysis and interpretation of data: SB, ML, MB, AT, GM, ST, NC, CF, FD, BC, ACl, MF, ACo, SA, EE, JFP, BL. Writing or substantial involvement in revision: SB, ML, SA, EE, JFP, BL.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

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

  • Data availability statement Data are available on reasonable request.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.