{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:00:46Z","timestamp":1785427246862,"version":"3.56.0"},"reference-count":69,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Programa de Incentivo \u00e0 Pesquisa (PIP), Instituto Fernandes Figueira\/FIOCRUZ\/FIOTEC","award":["IFF-008-FIO-13-3-18-30"],"award-info":[{"award-number":["IFF-008-FIO-13-3-18-30"]}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["SEI-260003\/006082\/2024"],"award-info":[{"award-number":["SEI-260003\/006082\/2024"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"award":["SEI-260003\/006082\/2024"],"award-info":[{"award-number":["SEI-260003\/006082\/2024"]}],"id":[{"id":"https:\/\/ror.org\/03kk0s825","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["406857\/2022-9"],"award-info":[{"award-number":["406857\/2022-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"award":["406857\/2022-9"],"award-info":[{"award-number":["406857\/2022-9"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"publisher"}]},{"name":"CNPq\/PIBIC"},{"DOI":"10.13039\/501100002322","name":"CAPES","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Primary ciliary dyskinesia (PCD) is a rare and genetically heterogeneous disorder that remains underdiagnosed in low- and middle-income countries, largely due to limited access to specialized diagnostic tests. Genetic analysis has become an essential component of PCD diagnosis, particularly where functional and ultrastructural evaluations are unavailable. Methods: We conducted an investigational study including children and adolescents with clinical suspicion of PCD followed at a Brazilian tertiary center. Clinical characterization included detailed phenotyping and calculation of the PICADAR score. Molecular investigation was performed using exome sequencing as a frontline diagnostic approach. Results: Among 27 individuals evaluated, 10 (37%) received a confirmed molecular diagnosis of PCD. An additional 6 (22%) individuals had inconclusive molecular findings, mainly due to variants of uncertain significance (VUS), and were classified as likely PCD based on combined clinical and molecular evidence. Higher PICADAR scores were more frequently observed among individuals with confirmed or likely molecular diagnosis, with 9 of 10 confirmed cases presenting a score above 5. Beyond PCD-associated findings, exome sequencing also enabled the identification of clinically relevant additional diagnoses, including cystic fibrosis, FGFR3-related hypochondroplasia, and ACMG-reportable secondary finding involving BRCA2. Some unresolved cases may also reflect inherent technical limitations of exome sequencing, including restricted sensitivity for copy-number variants, suboptimal coverage of highly homologous or GC-rich regions, and limited detection of deep intronic and other variants. Additional factors include challenges in variant interpretation and incomplete knowledge of disease-associated genes. Conclusions: Frontline exome sequencing is a valuable diagnostic tool for PCD, particularly when integrated with robust clinical phenotyping. Clinical scoring systems such as PICADAR may help prioritize individuals for genetic testing and optimize diagnostic yield in resource-limited settings.<\/jats:p>","DOI":"10.3390\/genes17070767","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:06:34Z","timestamp":1782875194000},"page":"767","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Utility of NGS-Based Diagnosis in Primary Ciliary Dyskinesia: Experience from a Brazilian Pediatric Cohort at a Reference Center for Rare Diseases"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2146-5734","authenticated-orcid":false,"given":"Patr\u00edcia F. Barreto M.","family":"Costa","sequence":"first","affiliation":[{"name":"Setor de Pneumologia, Departamento de Pediatria, Instituto Fernandes Figueira (IFF\/FIOCRUZ), Servi\u00e7o de Refer\u00eancia para Doen\u00e7as Raras, Minist\u00e9rio da Sa\u00fade, Rio de Janeiro 22250-020, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3429-5964","authenticated-orcid":false,"given":"Danielle de Freitas F. M.","family":"Fins","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular\/Medicina Gen\u00f4mica, Centro de Gen\u00e9tica M\u00e9dica, Instituto Fernandes Figueira (IFF\/FIOCRUZ), Servi\u00e7o de Refer\u00eancia para Doen\u00e7as Raras, Minist\u00e9rio da Sa\u00fade, Rio de Janeiro 22250-020, RJ, Brazil"},{"name":"Instituto Nacional de Doen\u00e7as Raras (InRaras), Hospital das Cl\u00ednicas de Porto Alegre, Porto Alegre 90035-903, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"de Oliveira Moraes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular\/Medicina Gen\u00f4mica, Centro de Gen\u00e9tica M\u00e9dica, Instituto Fernandes Figueira (IFF\/FIOCRUZ), Servi\u00e7o de Refer\u00eancia para Doen\u00e7as Raras, Minist\u00e9rio da Sa\u00fade, Rio de Janeiro 22250-020, RJ, Brazil"},{"name":"Instituto Nacional de Doen\u00e7as Raras (InRaras), Hospital das Cl\u00ednicas de Porto Alegre, Porto Alegre 90035-903, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2958-5271","authenticated-orcid":false,"given":"Tania Wrobel","family":"Folescu","sequence":"additional","affiliation":[{"name":"Setor de Pneumologia, Departamento de Pediatria, Instituto Fernandes Figueira (IFF\/FIOCRUZ), Servi\u00e7o de Refer\u00eancia para Doen\u00e7as Raras, Minist\u00e9rio da Sa\u00fade, Rio de Janeiro 22250-020, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0596-4821","authenticated-orcid":false,"given":"Renata Wrobel Folescu","family":"Cohen","sequence":"additional","affiliation":[{"name":"Setor de Pneumologia, Departamento de Pediatria, Instituto Fernandes Figueira (IFF\/FIOCRUZ), Servi\u00e7o de Refer\u00eancia para Doen\u00e7as Raras, Minist\u00e9rio da Sa\u00fade, Rio de Janeiro 22250-020, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natana","family":"Chaves Rabelo","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular\/Medicina Gen\u00f4mica, Centro de Gen\u00e9tica M\u00e9dica, Instituto Fernandes Figueira (IFF\/FIOCRUZ), Servi\u00e7o de Refer\u00eancia para Doen\u00e7as Raras, Minist\u00e9rio da Sa\u00fade, Rio de Janeiro 22250-020, RJ, Brazil"},{"name":"Instituto Nacional de Doen\u00e7as Raras (InRaras), Hospital das Cl\u00ednicas de Porto Alegre, Porto Alegre 90035-903, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Azevedo Barreto","sequence":"additional","affiliation":[{"name":"Setor de Pneumologia, Departamento de Pediatria, Instituto Fernandes Figueira (IFF\/FIOCRUZ), Servi\u00e7o de Refer\u00eancia para Doen\u00e7as Raras, Minist\u00e9rio da Sa\u00fade, Rio de Janeiro 22250-020, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Vieira da Cunha Moreira","sequence":"additional","affiliation":[{"name":"Setor de Pneumologia, Departamento de Pediatria, Instituto Fernandes Figueira (IFF\/FIOCRUZ), Servi\u00e7o de Refer\u00eancia para Doen\u00e7as Raras, Minist\u00e9rio da Sa\u00fade, Rio de Janeiro 22250-020, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Barbosa Abdala","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular\/Medicina Gen\u00f4mica, Centro de Gen\u00e9tica M\u00e9dica, Instituto Fernandes Figueira (IFF\/FIOCRUZ), Servi\u00e7o de Refer\u00eancia para Doen\u00e7as Raras, Minist\u00e9rio da Sa\u00fade, Rio de Janeiro 22250-020, RJ, Brazil"},{"name":"Instituto Nacional de Doen\u00e7as Raras (InRaras), Hospital das Cl\u00ednicas de Porto Alegre, Porto Alegre 90035-903, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Naccarato Teixeira Lopes Andrade","sequence":"additional","affiliation":[{"name":"Setor de Pneumologia, Departamento de Pediatria, Instituto Fernandes Figueira (IFF\/FIOCRUZ), Servi\u00e7o de Refer\u00eancia para Doen\u00e7as Raras, Minist\u00e9rio da Sa\u00fade, Rio de Janeiro 22250-020, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Juan","family":"Llerena","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica Cl\u00ednica, Centro de Gen\u00e9tica M\u00e9dica, Instituto Fernandes Figueira (IFF\/FIOCRUZ), Servi\u00e7o de Refer\u00eancia para Doen\u00e7as Raras, Minist\u00e9rio da Sa\u00fade, Rio de Janeiro 22250-020, RJ, Brazil"},{"name":"Centro Universit\u00e1rio Arthur S\u00e1 Earp Neto\/Faculdade de Medicina de Petr\u00f3polis (UNIFASE), Petr\u00f3polis 25680-120, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7726-4301","authenticated-orcid":false,"given":"Dafne","family":"Horovitz","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica Cl\u00ednica, Centro de Gen\u00e9tica M\u00e9dica, Instituto Fernandes Figueira (IFF\/FIOCRUZ), Servi\u00e7o de Refer\u00eancia para Doen\u00e7as Raras, Minist\u00e9rio da Sa\u00fade, Rio de Janeiro 22250-020, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Eduarda","family":"Gomes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular\/Medicina Gen\u00f4mica, Centro de Gen\u00e9tica M\u00e9dica, Instituto Fernandes Figueira (IFF\/FIOCRUZ), Servi\u00e7o de Refer\u00eancia para Doen\u00e7as Raras, Minist\u00e9rio da Sa\u00fade, Rio de Janeiro 22250-020, RJ, Brazil"},{"name":"Instituto Nacional de Doen\u00e7as Raras (InRaras), Hospital das Cl\u00ednicas de Porto Alegre, Porto Alegre 90035-903, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayonara","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular\/Medicina Gen\u00f4mica, Centro de Gen\u00e9tica M\u00e9dica, Instituto Fernandes Figueira (IFF\/FIOCRUZ), Servi\u00e7o de Refer\u00eancia para Doen\u00e7as Raras, Minist\u00e9rio da Sa\u00fade, Rio de Janeiro 22250-020, RJ, Brazil"},{"name":"Instituto Nacional de Doen\u00e7as Raras (InRaras), Hospital das Cl\u00ednicas de Porto Alegre, Porto Alegre 90035-903, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kalyoncu, M.Y., Hjeij, R., Yanaz, M., Gulieva, A., Selcuk Balc\u0131, M., Karabulut, \u015e., Metin Cakar, N., Ergenekon, A.P., Erdem Eralp, E., and Gokdemir, Y. 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