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Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left–right asymmetry

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Abstract

Primary ciliary dyskinesia (PCD, MIM 242650) is characterized by recurrent infections of the respiratory tract due to reduced mucociliary clearance and by sperm immobility. Half of the affected offspring have situs inversus (reversed organs), which results from randomization of left-right (LR) asymmetry1. We previously localized to chromosome 5p a PCD locus containing DNAH5, which encodes a protein highly similar to the Chlamydomonas γ-dynein heavy chain2. Here we characterize the full-length 14-kb transcript of DNAH5. Sequence analysis in individuals with PCD with randomization of LR asymmetry identified mutations resulting in non-functional DNAH5 proteins.

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Figure 1: Early embryonic expression of murine Dnahc5 and axonemal phenotype resulting from DNAH5 mutations.

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Acknowledgements

We thank the affected individuals and their families for their participation in this study. We thank the German patient support group 'Kartagener Syndrom und Primäre Ciliäre Dyskinesie e.V.' and the UK PCD support group for their cooperation. We are grateful to S. Lehrack, R. Melkaoui, M. Petry and K. Rak for technical assistance. We also wish to thank H. Felix for the contribution of electron microscopic photographs and S.E. Antonarakis, J.L.C. Blouin, L. Bartoloni, A. Bush, E. Byrne, T. Willems and M. Jorissen for the contribution of DNA samples and clinical data. This work was supported by grants from the Deutsche Forschungsgemeinschaft (to H.O.), the B. Braun-Stiftung (to H.O.), the Wissenschaftliche Gesellschaft Freiburg (to H.O.), the US National Institutes of Health, the Medical Research Council of the UK, the Wellcome Trust, and Action Research.

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Author notes

  1. Heike Olbrich and Karsten Häffner: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatrics and Adolescent Medicine, Albert Ludwigs University, Freiburg, 79106, Germany

    Heike Olbrich, Karsten Häffner, Alexander Völkel, Andreas Volz, Gürsel Sasmaz, Friedhelm Hildebrandt & Heymut Omran

  2. Medizinische Hochschule Hannover, Germany

    Andreas Kispert

  3. Max-Planck Institute for Molecular Genetics, Berlin, Germany

    Richard Reinhardt, Steffen Hennig, Hans Lehrach & Ralf Sudbrak

  4. Ruhrland-Klinik, Essen, Germany

    Nikolaus Konietzko

  5. University of North Carolina at Chapel Hill, North Carolina, USA

    Maimoona Zariwala, Peadar G. Noone & Michael Knowles

  6. Department of Paediatrics and Child Health, Royal Free and University College, London, UK

    Hannah M. Mitchison, Maggie Meeks & Eddie M.K. Chung

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  1. Heike Olbrich
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  2. Karsten Häffner
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  7. Richard Reinhardt
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  8. Steffen Hennig
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  9. Hans Lehrach
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  10. Nikolaus Konietzko
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  11. Maimoona Zariwala
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  12. Peadar G. Noone
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  13. Michael Knowles
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  14. Hannah M. Mitchison
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  15. Maggie Meeks
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  16. Eddie M.K. Chung
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  17. Friedhelm Hildebrandt
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  18. Ralf Sudbrak
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  19. Heymut Omran
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Corresponding author

Correspondence to Heymut Omran.

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Olbrich, H., Häffner, K., Kispert, A. et al. Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left–right asymmetry. Nat Genet 30, 143–144 (2002). https://doi.org/10.1038/ng817

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  • DOI: https://doi.org/10.1038/ng817

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