Axonemal Symmetry Break, a New Ultrastructural Diagnostic Tool for Primary Ciliary Dyskinesia?

Fecha de publicación: 06/01/2022 Fecha Ahead of Print: 06/01/2022

Autores de IIS La Fe

• Rosana Blanco Mañez

  Autor

• Miguel Armengot Carceller

  Autor

• Teresa Jaijo Sanchís

  Autor

Participantes ajenos a IIS La Fe

• Vera-Sempere F

Grupos

• Biomedicina Molecular, Celular y Genómica

  

  Leader

  José María Millán Salvador

• Unidad mixta de investigación en enfermedades raras (CIPF)

  

  Leader

  José María Millán Salvador

Abstract

Diagnosis testing for primary ciliary dyskinesia (PCD) requires a combination of investigations that includes study of ciliary beat pattern by high-speed video-microscopy, genetic testing and assessment of the ciliary ultrastructure by transmission electron microscopy (TEM). Historically, TEM was considered to be the "gold standard" for the diagnosis of PCD. However, with the advances in molecular genetic techniques, an increasing number of PCD variants show normal ultrastructure and cannot be diagnosed by TEM. During ultrastructural assessment of ciliary biopsies of patients with suspicion of PCD, we observed an axonemal defect not previously described that affects peripheral doublets tilting. To further characterize this defect of unknown significance, we studied the ciliary axonemes by TEM from both PCD-confirmed patients and patients with other sino-pulmonary diseases. We detected peripheral doublets tilting in all the PCD patients, without any significant difference in the distribution of ciliary beat pattern or mutated gene. This defect was also present in those patients with normal ultrastructure PCD subtypes. We believe that the performance of axonemal asymmetry analysis would be helpful to enhance diagnosis of PCD.

Keywords

• ciliary axoneme; diagnosis; primary ciliary dyskinesia; transmission electron microscopy