The cause of bronchiectasis is unknown in ~40% cases. Primary ciliary dyskinesia (PCD) accounts for up to 10% but underdiagnosis is common.

The aim of this study was to screen a large international cohort of patients with bronchiectasis for disease-causing mutations in genes associated with motile cilia structure and function.

Patients with CT confirmed bronchiectasis were enrolled from 6 centres across Europe. People with known PCD were excluded.

Whole exome sequencing was conducted in 573 individuals with bronchiectasis. Variants were called using a custom pipeline of 770 genes known to be associated with ciliary dysfunction plus CFTR. Homozygous or likely compound heterozygous mutations with moderate to high impact were reported. A subset of patients received nasal brushings to verify results.

10 individuals (2%) had mutations in known PCD genes (DNAI2, OFD1, GAS2L2, DNAAF1, DNAH9, DNAH11 and HYDIN). DNAAF1, OFD1 and DNAH11 mutations were verified at functional level with high speed video, electron microscopy and immunofluorescence analysis. Four individuals had bi-allelic CFTR mutations.

An additional 9 individuals had mutations in putative PCD genes: 2 dynein heavy chains (DNAH2, DNAH7), 2 intraflagellar transport proteins (IFT122, IFT172) and 5 additional ciliary genes with varied functions that are being further investigated.

In this large cohort, inherited ciliopathies were identified as a likely cause of bronchiectasis in 4% of patients. Half the findings were in previously undescribed ciliopathy genes. The study is ongoing aiming to functionally characterise previously undescribed genetic contributors to bronchiectasis.