Advances in diagnostic electron microscopy for motile ciliopathies

Session

Clinical Diagnostic Imaging

Authors

Prof Amelia Shoemark (1, 2)

Affiliations

1. University of Dundee
2. Royal Brompton Hospital

Keywords

cilia, genetics, ultrastructure, epithelium, flagella, diagnosis, transmission electron microscopy, tomography, multi-disciplinary team, respiratory, bronchiectasis, paediatrics, genotype, dynein

Abstract text

Motile ciliopathies including Primary ciliary dyskinesia (PCD) are rare inherited conditions affecting approximately 1 in 7500 people. Defects in motile cilia result in failure to clear mucus from the respiratory tract. As a consequence, patients suffer from recurrent infections and ordinarily develop lung scarring (bronchiectasis) by adulthood. People with PCD experience from early in life daily wet cough, regular chest infections and upper airways symptoms such as chronic rhinitis, sinusitis and recurrent otitis media. Due to the role of cilia in the embryonic node during development approximately 50% sufferers have reversal of the internal organs (situs inversus) and up to 12% have complex cardiac disease. As adults individuals with PCD can experience infertility due to dysfunctional cilia in the fallopian tube and efferent duct and due to dysfunctional sperm flagella.

Diagnosis is made by sampling epithelium for the nose and using multiple testing modalities.  Diagnosis is confirmed by the identification of pathogenic mutations  in one of fifty known PCD genes or identification of a recognised ultrastructural defect by electron microscopy. Neither test is fully sensitive to detect and confirm PCD.

This presentation will cover hallmark electron microscopy (TEM) defects diagnostic of PCD and integration of TEM results with other molecular testing modalities. To improve the accuracy of diagnosis advanced techniques such as electron tomography or the use of deep learning artificial intelligence will be discussed.