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Volume 17
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10.3390/genes17070767
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Clinical Utility of NGS-Based Diagnosis in Primary Ciliary Dyskinesia: Experience from a Brazilian Pediatric Cohort at a Reference Center for Rare Diseases

by
Patrícia F. Barreto M. Costa
1,†,
Danielle de Freitas F. M. Fins
2,3,†,
Isabelle de Oliveira Moraes
2,3,
Tania Wrobel Folescu
1,
Renata Wrobel Folescu Cohen
1,
Natana Chaves Rabelo
2,3,
Leticia Azevedo Barreto
1,
Julia Vieira da Cunha Moreira
1,
Bianca Barbosa Abdala
2,3,
Mariana Naccarato Teixeira Lopes Andrade
1,
Juan Llerena Jr
4,5,
Dafne Horovitz
4,
Maria Eduarda Gomes
2,3,* and
Sayonara Gonzalez
2,3,*
1
Setor de Pneumologia, Departamento de Pediatria, Instituto Fernandes Figueira (IFF/FIOCRUZ), Serviço de Referência para Doenças Raras, Ministério da Saúde, Rio de Janeiro 22250-020, RJ, Brazil
2
Laboratório de Biologia Molecular/Medicina Genômica, Centro de Genética Médica, Instituto Fernandes Figueira (IFF/FIOCRUZ), Serviço de Referência para Doenças Raras, Ministério da Saúde, Rio de Janeiro 22250-020, RJ, Brazil
3
Instituto Nacional de Doenças Raras (InRaras), Hospital das Clínicas de Porto Alegre, Porto Alegre 90035-903, RS, Brazil
4
Unidade de Genética Clínica, Centro de Genética Médica, Instituto Fernandes Figueira (IFF/FIOCRUZ), Serviço de Referência para Doenças Raras, Ministério da Saúde, Rio de Janeiro 22250-020, RJ, Brazil
5
Centro Universitário Arthur Sá Earp Neto/Faculdade de Medicina de Petrópolis (UNIFASE), Petrópolis 25680-120, RJ, Brazil
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Genes 2026, 17(7), 767; https://doi.org/10.3390/genes17070767
Submission received: 22 May 2026 / Revised: 21 June 2026 / Accepted: 22 June 2026 / Published: 30 June 2026
(This article belongs to the Special Issue Genetic Diagnosis and Treatment of Rare Diseases)
Versions Notes

Abstract

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.
Keywords: primary ciliary dyskinesia; exome sequencing (ES); next-generation sequencing (NGS); bronchiectasis; ciliopathies; rare genetic diseases primary ciliary dyskinesia; exome sequencing (ES); next-generation sequencing (NGS); bronchiectasis; ciliopathies; rare genetic diseases

Share and Cite

MDPI and ACS Style

Costa, P.F.B.M.; Fins, D.d.F.F.M.; de Oliveira Moraes, I.; Folescu, T.W.; Cohen, R.W.F.; Chaves Rabelo, N.; Azevedo Barreto, L.; Vieira da Cunha Moreira, J.; Barbosa Abdala, B.; Naccarato Teixeira Lopes Andrade, M.; et al. Clinical Utility of NGS-Based Diagnosis in Primary Ciliary Dyskinesia: Experience from a Brazilian Pediatric Cohort at a Reference Center for Rare Diseases. Genes 2026, 17, 767. https://doi.org/10.3390/genes17070767

AMA Style

Costa PFBM, Fins DdFFM, de Oliveira Moraes I, Folescu TW, Cohen RWF, Chaves Rabelo N, Azevedo Barreto L, Vieira da Cunha Moreira J, Barbosa Abdala B, Naccarato Teixeira Lopes Andrade M, et al. Clinical Utility of NGS-Based Diagnosis in Primary Ciliary Dyskinesia: Experience from a Brazilian Pediatric Cohort at a Reference Center for Rare Diseases. Genes. 2026; 17(7):767. https://doi.org/10.3390/genes17070767

Chicago/Turabian Style

Costa, Patrícia F. Barreto M., Danielle de Freitas F. M. Fins, Isabelle de Oliveira Moraes, Tania Wrobel Folescu, Renata Wrobel Folescu Cohen, Natana Chaves Rabelo, Leticia Azevedo Barreto, Julia Vieira da Cunha Moreira, Bianca Barbosa Abdala, Mariana Naccarato Teixeira Lopes Andrade, and et al. 2026. "Clinical Utility of NGS-Based Diagnosis in Primary Ciliary Dyskinesia: Experience from a Brazilian Pediatric Cohort at a Reference Center for Rare Diseases" Genes 17, no. 7: 767. https://doi.org/10.3390/genes17070767

APA Style

Costa, P. F. B. M., Fins, D. d. F. F. M., de Oliveira Moraes, I., Folescu, T. W., Cohen, R. W. F., Chaves Rabelo, N., Azevedo Barreto, L., Vieira da Cunha Moreira, J., Barbosa Abdala, B., Naccarato Teixeira Lopes Andrade, M., Llerena Jr, J., Horovitz, D., Gomes, M. E., & Gonzalez, S. (2026). Clinical Utility of NGS-Based Diagnosis in Primary Ciliary Dyskinesia: Experience from a Brazilian Pediatric Cohort at a Reference Center for Rare Diseases. Genes, 17(7), 767. https://doi.org/10.3390/genes17070767

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