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Primary ciliary dyskinesia (PCD) is a rare disorder of mucociliary clearance resulting in chronic oto-sinopulmonary disease. While the prevalence worldwide is estimated to be 1:10 000–1:15 000, it may be much higher in certain communities, especially where consanguinity is more prevalent. In the British South Asian community, for example, the prevalence has been estimated at 1:2450, similar to that of cystic fibrosis among caucasians.1
In Thorax, Shoemark and colleagues2 describe PCD in a highly consanguineous UK South Asian community, due to homozygous missense variants in CCDC103, usually resulting in the loss of both outer and inner dynein arms. The investigators identified 86 patients of South Asian (primarily Pakistani) descent with clinical signs and symptoms of PCD from the UK National PCD Diagnostic and Management Services. These individuals had a compatible clinical phenotype, but diagnosis was complicated by the fact that many of the standard diagnostic tests for PCD had yielded variable and frequently normal results, including nasal nitric oxide, ciliary beat frequency and ciliary ultrastructure by transmission electron microscopy. Ultimately, next-generation sequencing confirmed a homozygous pathogenic variant, p.His154Pro, in CCDC103 in 16 (19%) of these 86 cases, from 12 independent families.
From a clinical perspective, this report by Shoemark and colleagues2 highlights two important issues in the diagnosis of PCD. The first is that the prevalence of PCD may be higher than previously appreciated in certain populations, particularly in highly consanguineous communities. Indeed, in this report, all 16 patients with homozygous CCDC103 p.His154Pro mutations were children of consanguineous parents. While this UK South Asian PCD cohort was enriched for the CCDC103 p.His154Pro mutation, a number of other PCD-causing mutations were also present, including CCDC40, DNAAF1, HEATR2, LRRC6, ZMYND10 and RSPH4A. A high prevalence of PCD with genetic heterogeneity has similarly been …
Contributors All authors contributed to the writing of this editorial. MR organised the team and outline and contributed the content on PCD diagnosis. MAZ contributed the content on variants of uncertain significance. LEO contributed the content on functional studies. All authors reviewed and approved the final version.
Funding Supported by National Institutes of Health grants 5U54HL096458-06 (MAZ and MR), 5R01HL071798 (MAZ and LEO), 5R01HL117836-04-05 (LEO and MAZ).
Disclaimer The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH.
Competing interests None declared.
Provenance and peer review Commissioned; externally peer reviewed.
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