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Genome sequencing reveals underdiagnosis of primary ciliary dyskinesia in bronchiectasis

Shoemark, Amelia; Griffin, Helen; Wheway, Gabrielle; Hogg, Claire; Lucas, Jane S; Genomics England Research, Consortium; Camps, Carme; ... Wood, SM; + view all (2022) Genome sequencing reveals underdiagnosis of primary ciliary dyskinesia in bronchiectasis. European Respiratory Journal , 60 (5) , Article 2200176. 10.1183/13993003.00176-2022. Green open access

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Abstract

BACKGROUND: Bronchiectasis can result from infectious, genetic, immunological and allergic causes. 60-80% of cases are idiopathic, but a well-recognised genetic cause is the motile ciliopathy, primary ciliary dyskinesia (PCD). Diagnosis of PCD has management implications including addressing comorbidities, implementing genetic and fertility counselling and future access to PCD-specific treatments. Diagnostic testing can be complex; however, PCD genetic testing is moving rapidly from research into clinical diagnostics and would confirm the cause of bronchiectasis. METHODS: This observational study used genetic data from severe bronchiectasis patients recruited to the UK 100,000 Genomes Project and patients referred for gene panel testing within a tertiary respiratory hospital. Patients referred for genetic testing due to clinical suspicion of PCD were excluded from both analyses. Data were accessed from the British Thoracic Society audit, to investigate whether motile ciliopathies are underdiagnosed in people with bronchiectasis in the UK. RESULTS: Pathogenic or likely pathogenic variants were identified in motile ciliopathy genes in 17 (12%) out of 142 individuals by whole-genome sequencing. Similarly, in a single centre with access to pathological diagnostic facilities, 5-10% of patients received a PCD diagnosis by gene panel, often linked to normal/inconclusive nasal nitric oxide and cilia functional test results. In 4898 audited patients with bronchiectasis, <2% were tested for PCD and <1% received genetic testing. CONCLUSIONS: PCD is underdiagnosed as a cause of bronchiectasis. Increased uptake of genetic testing may help to identify bronchiectasis due to motile ciliopathies and ensure appropriate management.

Type: Article
Title: Genome sequencing reveals underdiagnosis of primary ciliary dyskinesia in bronchiectasis
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1183/13993003.00176-2022
Publisher version: https://doi.org/10.1183/13993003.00176-2022
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: Bronchiectasis, Cilia, Ciliary Motility Disorders, Ciliopathies, Humans, Kartagener Syndrome, Mutation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10160898
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