{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:11:35Z","timestamp":1790629895368,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T00:00:00Z","timestamp":1700265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010564","name":"German Center for Lung Research","doi-asserted-by":"publisher","award":["82DZL002A1"],"award-info":[{"award-number":["82DZL002A1"]}],"id":[{"id":"10.13039\/501100010564","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Novartis AG","award":["82DZL002A1"],"award-info":[{"award-number":["82DZL002A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Whole-exome sequencing has expedited the diagnostic work-up of primary ciliary dyskinesia (PCD), when used in addition to clinical phenotype and nasal nitric oxide. However, it reveals variants of uncertain significance (VUS) in established PCD genes or (likely) pathogenic variants in genes of uncertain significance in approximately 30% of tested individuals. We aimed to assess genotype\u2013phenotype correlations in adults with bronchiectasis, clinical suspicion of PCD, and inconclusive whole-exome sequencing results using transmission electron microscopy (TEM) and ciliary image averaging by the PCD Detect software. We recruited 16 patients with VUS in CCDC39, CCDC40, CCDC103, DNAH5, DNAH5\/CCDC40, DNAH8\/HYDIN, DNAH11, and DNAI1 as well as variants in the PCD candidate genes DNAH1, DNAH7, NEK10, and NME5. We found normal ciliary ultrastructure in eight patients with VUS in CCDC39, DNAH1, DNAH7, DNAH8\/HYDIN, DNAH11, and DNAI1. In six patients with VUS in CCDC40, CCDC103, DNAH5, and DNAI1, we identified a corresponding ultrastructural hallmark defect. In one patient with homozygous variant in NME5, we detected a central complex defect supporting clinical relevance. Using TEM as a targeted approach, we established important genotype\u2013phenotype correlations and definite PCD in a considerable proportion of patients. Overall, the PCD Detect software proved feasible in support of TEM.<\/jats:p>","DOI":"10.3390\/cells12222651","type":"journal-article","created":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T07:33:18Z","timestamp":1700292798000},"page":"2651","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Ciliary Ultrastructure Assessed by Transmission Electron Microscopy in Adults with Bronchiectasis and Suspected Primary Ciliary Dyskinesia but Inconclusive Genotype"],"prefix":"10.3390","volume":"12","author":[{"given":"Ben O.","family":"Staar","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School (MHH), 30625 Hannover, Germany"},{"name":"Biomedical Research in End-Stage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), 30625 Hannover, Germany"},{"name":"European Reference Network for Rare and Complex Lung Diseases (ERN-LUNG), 60596 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Hegermann","sequence":"additional","affiliation":[{"name":"Biomedical Research in End-Stage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), 30625 Hannover, Germany"},{"name":"Research Core Unit Electron Microscopy, Institute of Functional and Applied Anatomy, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1880-291X","authenticated-orcid":false,"given":"Bernd","family":"Auber","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Ewen","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School (MHH), 30625 Hannover, Germany"},{"name":"Biomedical Research in End-Stage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), 30625 Hannover, Germany"},{"name":"European Reference Network for Rare and Complex Lung Diseases (ERN-LUNG), 60596 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"von Hardenberg","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Olmer","sequence":"additional","affiliation":[{"name":"Biomedical Research in End-Stage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), 30625 Hannover, Germany"},{"name":"Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Hannover Medical School (MHH), 30625 Hannover, Germany"},{"name":"REBIRTH\u2014Research Center for Translational and Regenerative Medicine, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabell","family":"Pink","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School (MHH), 30625 Hannover, Germany"},{"name":"Biomedical Research in End-Stage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), 30625 Hannover, Germany"},{"name":"European Reference Network for Rare and Complex Lung Diseases (ERN-LUNG), 60596 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Rademacher","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School (MHH), 30625 Hannover, Germany"},{"name":"Biomedical Research in End-Stage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), 30625 Hannover, Germany"},{"name":"European Reference Network for Rare and Complex Lung Diseases (ERN-LUNG), 60596 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Wetzke","sequence":"additional","affiliation":[{"name":"Biomedical Research in End-Stage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), 30625 Hannover, Germany"},{"name":"Department of Paediatric Pneumology, Allergology and Neonatology, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9084-4968","authenticated-orcid":false,"given":"Felix C.","family":"Ringshausen","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School (MHH), 30625 Hannover, Germany"},{"name":"Biomedical Research in End-Stage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), 30625 Hannover, Germany"},{"name":"European Reference Network for Rare and Complex Lung Diseases (ERN-LUNG), 60596 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/s41572-020-0209-6","article-title":"Motile ciliopathies","volume":"6","author":"Wallmeier","year":"2020","journal-title":"Nat. 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