Genome sequencing reveals underdiagnosis of primary ciliary dyskinesia in bronchiectasis.
Journal
The European respiratory journal
ISSN: 1399-3003
Titre abrégé: Eur Respir J
Pays: England
ID NLM: 8803460
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
25
01
2022
accepted:
12
05
2022
pubmed:
22
6
2022
medline:
22
11
2022
entrez:
21
6
2022
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 35728977
pii: 13993003.00176-2022
doi: 10.1183/13993003.00176-2022
pii:
doi:
Types de publication
Observational Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : MC_EX_MR/M009203/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_14089
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M009203/1
Pays : United Kingdom
Informations de copyright
Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.
Déclaration de conflit d'intérêts
Conflict of interest: A. Shoemark has received grants from AstraZeneca. G. Wheway is currently employed by Illumina Inc. M.R. Loebinger has received consultancy or speaker fees from Insmed, AstraZeneca, Parion, Grifols and Armata. J.D. Chalmers has received grants or contracts from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Novartis and Insmed; and received consultancy or speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Insmed, Janssen, Novartis and Zambon. J.S. Lucas reports grants from NHS England, NIHR and AIR Charity. H.M. Mitchison is a Trustee of Ciliopathy Alliance. A. De Soyza reports grants from AstraZeneca, GlaxoSmithKline and Pfizer; consulting fees and lecture honoraria from Gilead, GlaxoSmithKline, AstraZeneca, LifeArc and 30T; participation on advisory board at Bayer; receipt of equipment from GlaxoSmithKline. All other authors have nothing to disclose.