{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T03:54:48Z","timestamp":1783396488177,"version":"3.54.6"},"reference-count":40,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["CNPq: #471078\/2014-0 and #302608\/2016-8"],"award-info":[{"award-number":["CNPq: #471078\/2014-0 and #302608\/2016-8"]}]},{"name":"the Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["FAPESP: #2015\/12858-5"],"award-info":[{"award-number":["FAPESP: #2015\/12858-5"]}]},{"name":"the S\u00e3o Paulo research Foundation","award":["CNPq: #471078\/2014-0 and #302608\/2016-8"],"award-info":[{"award-number":["CNPq: #471078\/2014-0 and #302608\/2016-8"]}]},{"name":"the S\u00e3o Paulo research Foundation","award":["FAPESP: #2015\/12858-5"],"award-info":[{"award-number":["FAPESP: #2015\/12858-5"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Primary ciliary dyskinesia (PCD) causes cellular cilia motility alterations, leading to clinical manifestations in the upper and lower respiratory tract and situs abnormalities. The PCD diagnosis was improved after the inclusion of diagnostic tools, such as transmission electron microscopy and genetic screening; however, the PCD screening is a challenge yet. In this context, we aimed to describe the clinical, genetic, and ultra-ciliary characteristics in individuals with clinical suspicion of PCD (cPCD) from a Brazilian Tertiary Hospital. An observational study was carried out with individuals during the follow-up between 2011 and 2021. The individuals were submitted to clinical questionnaires, transmission electron microscopy, and genetic screening for pathogenic variants in PCD-related genes. Those patients were classified according to the degree of suspicion for PCD. In our study, we enrolled thirty-seven cPCD individuals; 20\/37 (54.1%) had chronic rhinosinusitis, 28\/37 (75.6%) had bronchiectasis, and 29\/37 (78.4%) had recurrent pneumonia. A total of 17\/37 (45.9%) individuals had transmission electron microscopy or genetic confirmation of PCD; 10 individuals had at least one positive pathogenic genetic variant in the PCD-related genes; however, only seven patients presented a conclusive result according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology with two pathogenic variants in homozygous or compound heterozygous. The median age at diagnosis was 13 years, and the median time between suspicion and diagnosis was four years. Sixteen patients had class I electron microscopy alterations, seven had class II alterations, and 14 had normal transmission electron microscopy according to the international consensus guideline for reporting transmission electron microscopy results in the diagnosis of PCD (BEAT-PCD TEM Criteria). Genetic screening for pathogenic variants in PCD-related genes and transmission electron microscopy can help determine the PCD diagnosis; however, they are still unavailable to all individuals with clinical suspicion in Brazil. We described ultrastructural alterations found in our population along with the identification of pathogenic variants in PCD-related genes.<\/jats:p>","DOI":"10.3390\/genes13071252","type":"journal-article","created":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T21:00:28Z","timestamp":1658091628000},"page":"1252","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Challenges in Diagnosing Primary Ciliary Dyskinesia in a Brazilian Tertiary Hospital"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5294-3698","authenticated-orcid":false,"given":"Mariana Dalbo Contrera","family":"Toro","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, Faculty of Medical Sciences, University of Campinas, Tess\u00e1lia Vieira de Camargo, 126, Cidade Universit\u00e1ria Zeferino Vaz, Campinas, S\u00e3o Paulo 13083-887, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3387-5642","authenticated-orcid":false,"given":"Jos\u00e9 Dirceu","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medical Sciences, University of Campinas, Tess\u00e1lia Vieira de Camargo, 126, Cidade Universit\u00e1ria Zeferino Vaz, Campinas, S\u00e3o Paulo 13083-887, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4955-4234","authenticated-orcid":false,"given":"Fernando Augusto Lima","family":"Marson","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics and Genome Medicine, Department of Medical Genetics, Faculty of Medical Sciences, University of Campinas, Tess\u00e1lia Vieira de Camargo, 126, Cidade Universit\u00e1ria Zeferino Vaz, Campinas, S\u00e3o Paulo 13083-887, Brazil"},{"name":"Laboratory of Human and Medical Genetics, Laboratory of Cell and Molecular Tumor Biology and Bioactive Compounds, S\u00e3o Francisco University, Avenida S\u00e3o Francisco de Assis, 218, Jardim S\u00e3o Jos\u00e9, Bragan\u00e7a Paulista, S\u00e3o Paulo 12916-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9rica","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Faculty of Medical Sciences, University of Campinas, Tess\u00e1lia Vieira de Camargo, 126, Cidade Universit\u00e1ria Zeferino Vaz, Campinas, S\u00e3o Paulo 13083-887, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adyl\u00e9ia Aparecida Dalbo Contrera","family":"Toro","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medical Sciences, University of Campinas, Tess\u00e1lia Vieira de Camargo, 126, Cidade Universit\u00e1ria Zeferino Vaz, Campinas, S\u00e3o Paulo 13083-887, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen Silvia","family":"Bertuzzo","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics and Genome Medicine, Department of Medical Genetics, Faculty of Medical Sciences, University of Campinas, Tess\u00e1lia Vieira de Camargo, 126, Cidade Universit\u00e1ria Zeferino Vaz, Campinas, S\u00e3o Paulo 13083-887, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus Herbert","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pontifical Catholic University of Rio Grande do Sul, Av. Ipiranga, 6681, Porto Alegre 90619-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5963-912X","authenticated-orcid":false,"given":"Eul\u00e1lia","family":"Sakano","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Faculty of Medical Sciences, University of Campinas, Tess\u00e1lia Vieira de Camargo, 126, Cidade Universit\u00e1ria Zeferino Vaz, Campinas, S\u00e3o Paulo 13083-887, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e24","DOI":"10.1164\/rccm.201805-0819ST","article-title":"Diagnosis of Primary Ciliary Dyskinesia. An Official American Thoracic Society Clinical Practice Guideline","volume":"197","author":"Shapiro","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1601090","DOI":"10.1183\/13993003.01090-2016","article-title":"European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia","volume":"49","author":"Lucas","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/S2213-2600(19)30374-1","article-title":"Review Primary ciliary dyskinesia in the genomics age","volume":"8","author":"Lucas","year":"2020","journal-title":"Lancet Respir."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1183\/13993003.00736-2016","article-title":"Clinical manifestations in primary ciliary dyskinesia: Systematic review and meta-analysis","volume":"48","author":"Goutaki","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4193\/Rhin20.401","article-title":"European position paper on rhinosinusitis and nasal polyps","volume":"58","author":"Fokkens","year":"2020","journal-title":"Rhinology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1126\/science.1084576","article-title":"A Human Syndrome Caused by Immotile Cilia","volume":"193","author":"Afzelius","year":"1976","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1183\/09031936.00175614","article-title":"Diagnosis of primary ciliary dyskinesia: Searching for a gold standard","volume":"44","author":"Lucas","year":"2014","journal-title":"Eur. Respir. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1901066","DOI":"10.1183\/13993003.01066-2019","article-title":"ERS and ATS diagnostic guidelines for primary ciliary dyskinesia: Similarities and differences in approach to diagnosis","volume":"54","author":"Shoemark","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1164\/rccm.201907-1489LE","article-title":"Reply to Shoemark et al. And to Shapiro et al","volume":"201","author":"Amirav","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1513\/AnnalsATS.201511-748OC","article-title":"Clinical Features and Associated Likelihood of Primary Ciliary Dyskinesia in Children and Adolescents","volume":"13","author":"Leigh","year":"2016","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1183\/13993003.01551-2015","article-title":"PICADAR: A diagnostic predictive tool for primary ciliary dyskinesia","volume":"47","author":"Behan","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Martin\u016f, V., Bo\u0159ek-Dohalsk\u00e1, L., Var\u00e9nyiov\u00e1, \u017d., Uhl\u00edk, J., \u010capek, V., Pohunek, P., and Kouck\u00fd, V. (2021). Evaluation of a Clinical Index as a Predictive Tool for Primary Ciliary Dyskinesia. Diagnostics, 11.","DOI":"10.3390\/diagnostics11061088"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.chest.2019.01.036","article-title":"Accuracy of High-Speed Video Analysis to Diagnose Primary Ciliary Dyskinesia","volume":"155","author":"Rubbo","year":"2019","journal-title":"Chest"},{"key":"ref_14","first-page":"34","article-title":"CON: Primary Ciliary Dyskinesia diagnosis: Genes are all you need!","volume":"37","author":"Hogg","year":"2021","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_15","first-page":"32","article-title":"PRO: Primary Ciliary Dyskinesia: Genes are all you need!","volume":"37","author":"Shirlow","year":"2021","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1601181","DOI":"10.1183\/13993003.01181-2016","article-title":"The international primary ciliary dyskinesia cohort (iPCD Cohort): Methods and first results","volume":"49","author":"Goutaki","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"160058","DOI":"10.1183\/16000617.0058-2016","article-title":"Diagnosis of primary ciliary dyskinesia: Potential options for resource-limited countries","volume":"26","author":"Rumman","year":"2017","journal-title":"Eur. Respir. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Piatti, G., De Santi, M.M., Farolfi, A., Zuccotti, G.V., D\u2019Auria, E., Patria, M.F., Torretta, S., Consonni, D., and Ambrosetti, U. (2020). Exacerbations and Pseudomonas aeruginosa colonization are associated with altered lung structure and function in primary ciliary dyskinesia. BMC Pediatr., 20.","DOI":"10.1186\/s12887-020-02062-4"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8693","DOI":"10.1038\/s41598-019-45017-1","article-title":"Severe pulmonary disease in an adult primary ciliary dyskinesia population in Brazil","volume":"9","author":"Olm","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1183\/20734735.008517","article-title":"Diagnosis of primary ciliary dyskinesia: Summary of the ERS Task Force report","volume":"13","author":"Kuehni","year":"2017","journal-title":"Breathe"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1900725","DOI":"10.1183\/13993003.00725-2019","article-title":"International consensus guideline for reporting transmission electron microscopy results in the diagnosis of primary ciliary dyskinesia (BEAT PCD TEM Criteria)","volume":"55","author":"Shoemark","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1590\/S1806-37132015000004447","article-title":"Diagnosis of primary ciliary dyskinesia","volume":"41","author":"Olm","year":"2015","journal-title":"J. Bras. Pneumol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.otorri.2009.01.013","article-title":"Discinesia ciliar primaria. Ciliopat\u00edas","volume":"61","author":"Carceller","year":"2010","journal-title":"Acta Otorrinolaringol. Esp."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1750-1172-9-11","article-title":"Primary ciliary dyskinesia: Critical evaluation of clinical symptoms and diagnosis in patients with normal and abnormal ultrastructure","volume":"9","author":"Boone","year":"2014","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1513\/AnnalsATS.201605-331PS","article-title":"Toward an earlier diagnosis of primary ciliary dyskinesia which patients should undergo detailed diagnostic testing?","volume":"13","author":"Kuehni","year":"2016","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_27","first-page":"19","article-title":"Primary ciliary dyskinesia among Arabs: Where do we go from here?","volume":"29","author":"Hammoudeh","year":"2019","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1183\/09031936.00001010","article-title":"Factors influencing age at diagnosis of primary ciliary dyskinesia in European children","volume":"36","author":"Kuehni","year":"2010","journal-title":"Eur. Respir. J."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Goutaki, M., Halbeisen, F., Barbato, A., Crowley, S., Harris, A., Hirst, R., Karadag, B., Martinu, V., Morgan, L., and O\u2019Callaghan, C. (2020). Late Diagnosis of Infants with PCD and Neonatal Respiratory Distress. J. Clin. Med., 9.","DOI":"10.3390\/jcm9092871"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1183\/13993003.02018-2015","article-title":"Diagnosing primary ciliary dyskinesia: An international patient perspective","volume":"48","author":"Behan","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1007\/s11136-017-1564-y","article-title":"The patient\u2019s experience of primary ciliary dyskinesia: A systematic review","volume":"26","author":"Behan","year":"2017","journal-title":"Qual. Life Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1164\/rccm.200601-084OC","article-title":"DNAH5Mutations Are a Common Cause of Primary Ciliary Dyskinesia with Outer Dynein Arm Defects","volume":"174","author":"Hornef","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1164\/rccm.200411-1583OC","article-title":"Mislocalization of DNAH5 and DNAH9 in Respiratory Cells from Patients with Primary Ciliary Dyskinesia","volume":"171","author":"Fliegauf","year":"2005","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1136\/jmg.2008.061176","article-title":"Mutations in DNAH5 account for only 15% of a non-preselected cohort of patients with primary ciliary dyskinesia","volume":"46","author":"Failly","year":"2009","journal-title":"J. Med. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1080\/01913123.2017.1362088","article-title":"Value of transmission electron microscopy for primary ciliary dyskinesia diagnosis in the era of molecular medicine: Genetic defects with normal and non-diagnostic ciliary ultrastructure","volume":"41","author":"Shapiro","year":"2017","journal-title":"Ultrastruct. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1136\/thoraxjnl-2011-200301","article-title":"Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure","volume":"67","author":"Knowles","year":"2012","journal-title":"Thorax"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.ajhg.2014.08.005","article-title":"CCDC151 Mutations Cause Primary Ciliary Dyskinesia by Disruption of the Outer Dynein Arm Docking Complex Formation","volume":"95","author":"Hjeij","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.ajhg.2013.06.009","article-title":"ARMC4 Mutations Cause Primary Ciliary Dyskinesia with Randomization of Left\/Right Body Asymmetry","volume":"93","author":"Hjeij","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1136\/jmedgenet-2012-100867","article-title":"Delineation of CCDC39\/CCDC40 mutation spectrum and associated phenotypes in primary ciliary dyskinesia","volume":"49","author":"Blanchon","year":"2012","journal-title":"J. Med. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"163","DOI":"10.4172\/2157-7412.1000163","article-title":"Inner Dynein Arm Defects in Primary Ciliary Dyskinesia","volume":"4","author":"Shoemark","year":"2013","journal-title":"J. Genet. Syndr. Gene Ther."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/7\/1252\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:51:20Z","timestamp":1760140280000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/7\/1252"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,15]]},"references-count":40,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["genes13071252"],"URL":"https:\/\/doi.org\/10.3390\/genes13071252","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,15]]}}}