Background: CEP164 encodes a centrosomal protein required for assembly of primary cilia. More recently it has been suggested it may also have a role in formation of multiple motile cilia. Pathogenic variants in CEP164 are known to cause nephronophthisis-related ciliopathies but a causative link to the motile ciliopathy primary ciliary dyskinesia (PCD) has not been proven.

Aim: To assess airway cilia in a patient with a clinical history consistent with PCD, and bi-allelic variants in CEP164.

Method: A patient with bronchiectasis in the UK 100,000 Genomes Project was found to have compound heterozygous stop gain variants in CEP164, and no other relevant variants. The patient underwent PCD diagnostic functional testing including high-speed video microscopy and transmission electron microscopy (TEM) of nasal epithelial cells. In addition, localisation of CEP164 protein was assessed by immunofluorescence (IF).

Results: Cilia displayed a dyskinetic ciliary beat pattern, with long cilia and cilia with bulbous tips. Air liquid interface culture partially resolved dyskinesia, however an abnormal ?staggered? beat pattern was evident and the presence of long cilia persisted. Ciliary ultrastructure was normal by TEM.  IF analysis demonstrated an absence of CEP164 labelling at the centriolar region.

Conclusion: Supported by BEAT-PCD, we provide evidence that presence of CEP164 is vital to correct formation and function of respiratory cilia in addition to primary cilia, and that pathogenic variants in CEP164 are responsible for the PCD phenotype in this patient. We suggest CEP164 should be considered a candidate gene for PCD.