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Genetic Spectrum and Clinical Characteristics of Patients with Primary Ciliary Dyskinesia: a Belgian Single Center Study

  • PRIMARY CILIARY DYSKINESIA
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Abstract

Purpose

We aimed to examine the correlation between clinical characteristics and the pathogenic gene variants in patients with Primary Ciliary Dyskinesia (PCD).

Methods

We conducted a retrospective single-center study in patients with PCD followed at the University Hospitals Leuven. We included patients with genetically confirmed PCD and described their genotype, data from ultrastructural ciliary evaluation and clinical characteristics. Genotype/phenotype correlations were studied in patients with the most frequently involved genes.

Results

We enrolled 74 patients with a median age of 25.58 years. The most frequently involved genes were DNAH11 (n = 23) and DNAH5 (n = 19). The most frequent types of pathogenic variants were missense (n = 42) and frameshift variants (n = 36) and most patients had compound heterozygous variants (n = 44). Ciliary ultrastructure (p < 0.001), situs (p = 0.015) and age at diagnosis (median 9.50 vs 4.71 years, p = 0.037) differed between DNAH11 and DNAH5. When correcting for situs this difference in age at diagnosis was no longer significant (p = 0.973). Patients with situs inversus were diagnosed earlier (p = 0.031). Respiratory tract microbiology (p = 0.161), lung function (cross-sectional, p = 0.829 and longitudinal, p = 0.329) and chest CT abnormalities (p = 0.202) were not significantly different between DNAH11 and DNAH5 variants.

Conclusion

This study suggests a genotype–phenotype correlation for some of the evaluated clinical characteristics of the two most frequently involved genes in this study, namely DNAH11 and DNAH5.

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Data Availability

No datasets were generated or analysed during the current study.

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Acknowledgements

Mieke Boon participates in the European Reference Network for Rare Respiratory Diseases (ERN-LUNG) (739546) and in the “BEAT-PCD clinical research collaboration, supported by the European Respiratory Society.”

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Pediatrics, Pediatric Pulmonology, University Hospital of Leuven, Herestraat 49, 3000, Leuven, Belgium

    Noelia Rodriguez Mier, Marijke Proesmans, François Vermeulen & Mieke Boon

  2. Department of Neurosciences, Research Group Experimental Oto-Rhino-Laryngology, KU Leuven, Leuven, Belgium

    Martine Jaspers & Mark Jorissen

  3. Center for Human Genetics, University Hospital of Leuven, Leuven, Belgium

    Evelien Van Hoof & Jeroen Breckpot

  4. Department of Otorhinolaryngology, University Hospital of Leuven, Leuven, Belgium

    Mark Jorissen

  5. Department of Pulmonology, University Hospital of Leuven, Leuven, Belgium

    Natalie Lorent

Authors
  1. Noelia Rodriguez Mier
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  2. Martine Jaspers
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  3. Evelien Van Hoof
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  9. Mieke Boon
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Contributions

Noelia Rodriguez Mier: data curation, formal analysis, investigation, methodology, writing. Martine Jaspers: data curation and methodology. Evelien Van Hoof: data curation and methodology. Mark Jorissen: review and editing. Natalie Lorent: validation, review and editing. Marijke Proesmans: validation, review and editing. François Vermeulen: validation, review and editing. Jeroen Breckpot: validation, review and editing. Mieke Boon: conceptualization, methodology, formal analysis, investigation, supervision, validation, writing.

Corresponding author

Correspondence to Noelia Rodriguez Mier.

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Rodriguez Mier, N., Jaspers, M., Van Hoof, E. et al. Genetic Spectrum and Clinical Characteristics of Patients with Primary Ciliary Dyskinesia: a Belgian Single Center Study. Lung (2024). https://doi.org/10.1007/s00408-024-00696-0

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