Related Experiment Video

Updated: Jun 19, 2025

High-speed Video Microscopy Analysis for First-line Diagnosis of Primary Ciliary Dyskinesia
05:32

High-speed Video Microscopy Analysis for First-line Diagnosis of Primary Ciliary Dyskinesia

Published on: January 19, 2022

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Primary Ciliary Dyskinesia Associated Disease-Causing Variants in CCDC39 and CCDC40 Cause Axonemal Absence of Inner

Alina Wilken1, Inga Marlena Höben1, Alexander Wolter2

  • 1Department of General Pediatrics, University Hospital Muenster, 48149 Muenster, Germany.

Cells
|July 26, 2024
PubMed

Insights

Genetic variants in CCDC39 and CCDC40 cause primary ciliary dyskinesia (PCD) by disrupting the ciliary axonemal ruler. This study reveals the absence of key inner dynein arm (IDA) proteins in respiratory cilia, impacting diagnostics.

Area of Science:

  • Cell Biology
  • Genetics
  • Respiratory Medicine

Background:

  • Primary ciliary dyskinesia (PCD) is a hereditary respiratory disorder.
  • Bi-allelic variants in CCDC39 and CCDC40 genes cause PCD by affecting the ciliary axonemal molecular ruler.
  • Defects lead to abnormal ciliary beating, respiratory infections, and axonemal disorganization.

Purpose of the Study:

  • To molecularly characterize defects in the 96 nm axonemal ruler caused by CCDC39 and CCDC40 variants.
  • To analyze the impact of these variants on other axonemal components.
  • To improve diagnostics for axonemal ruler defects in PCD.

Main Methods:

  • Next-generation sequencing to identify individuals with CCDC39/CCDC40 variants.
  • Immunofluorescence analysis of respiratory ciliary axonemes.
  • Molecular characterization of protein assembly defects.

Main Results:

  • Identified 51 individuals with disease-causing CCDC39/CCDC40 variants.
  • Demonstrated conspicuous absence of IDA heavy chains DNAH1, DNAH6, and DNAH7 in respiratory cilia.
  • Showed that centrin2 (CETN2)-containing IDAs are also affected.

Conclusions:

  • CCDC39 and CCDC40 are crucial for the assembly and function of inner dynein arms (IDAs) in human respiratory cilia.
  • The study identifies IDA defects as a key molecular consequence of CCDC39/CCDC40 variants.
  • Findings enhance the diagnostics of axonemal ruler defects by characterizing associated IDA abnormalities.

Keywords:
IDAPCDaxonemal disorganizationdiagnosticsmotile ciliaruler

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