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PCD is a disorder caused by mutations in genes required for motile cilium structure or function, resulting in impaired mucociliary clearance. Symptoms appear in infancy but diagnosis is often late or missed, often due to the lack of a \u201cgold standard\u201d diagnostic tool and non-specific symptoms. Mutations in\u2009&gt;\u200950 genes account for around 70% of cases, with additional genes, and non-coding, synonymous, missense changes or structural variants (SVs) in known genes presumed to account for the missing heritability.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>UK patients with no identified genetic confirmation for the cause of their PCD or bronchiectasis were eligible for whole genome sequencing (WGS) in the Genomics England Ltd 100,000 Genomes Project. 21 PCD probands and 52 non-cystic fibrosis (CF) bronchiectasis probands were recruited in Wessex Genome Medicine Centre (GMC). We carried out analysis of single nucleotide variants (SNVs) and SVs in all families recruited in Wessex GMC.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>16\/21 probands in the PCD cohort received confirmed (n\u2009=\u20099), probable (n\u2009=\u20094) or possible (n\u2009=\u20093) diagnosis from WGS, although 13\/16 of these could have been picked up by current standard of care gene panel testing. In the other cases, SVs were identified which were missed by panel testing. We identified variants in novel PCD candidate genes (<jats:italic>IFT140<\/jats:italic> and <jats:italic>PLK4<\/jats:italic>) in 2 probands in the PCD cohort. 3\/52 probands in the non-CF bronchiectasis cohort received a confirmed (n\u2009=\u20092) or possible (n\u2009=\u20091) diagnosis of PCD. We identified variants in novel PCD candidate genes (<jats:italic>CFAP53<\/jats:italic> and <jats:italic>CEP164<\/jats:italic>) in 2 further probands in the non-CF bronchiectasis cohort.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Genetic testing is an important component of diagnosing PCD, especially in cases of atypical disease history. WGS is effective in cases where prior gene panel testing has found no variants or only heterozygous variants. In these cases it may detect SVs and is a powerful tool for novel gene discovery.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12920-021-01084-w","type":"journal-article","created":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T23:05:23Z","timestamp":1632438323000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Whole genome sequencing in the diagnosis of primary ciliary dyskinesia"],"prefix":"10.1186","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0494-0783","authenticated-orcid":false,"given":"Gabrielle","family":"Wheway","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. 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GW was granted access to the 100,000 Genomes Project research environment by the Genomics England Access Review Committee, as part of the Hearing and Sight, Neurology and Paediatrics Genomics England Clinical Interpretation Partnerships (GeCIPs). Within the 100,000 Genomes Project research environment, research project RR185 \u2018Study of cilia and ciliopathy genes across the 100,000 GP cohort\u2019 was registered by GW and approved by Genomics England. This research study received ethical approval from University of Southampton Faculty of Medicine Ethics Committee (ERGO#54400). Further written informed\u00a0consent was obtained from all participants (or parent\/ legal guardian) recruited for PCD diagnostic testing (National Research Ethics Service South Central (A) Committee 07\/Q1702\/109) and University of Southampton Faculty of Medicine Ethics Committee ERGO #53155.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from all participants, or their parents if\u2009<\u200918\u00a0years of age, recruited to the 100,000 Genomes Project for data and clinical details to be used for research and publication as part of the informed consent process (IRAS ID 166046; REC reference 14\/EE\/1112).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publication"}},{"value":"JSL reports grants, personal fees and non-financial support from Circassia. GW is employed by Illumina Inc. Other authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"234"}}