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Duplications of noncoding elements 5′ of SOX9 are associated with brachydactyly-anonychia

Nature Genetics volume 41, pages 862–863 (2009)Cite this article

To the Editor:

In a recent Nature Genetics letter, Benko et al.1 describe a series of changes in noncoding elements 5′ and 3′ of SOX9 in individuals with Pierre Robin sequence, a condition characterized by micrognathia, glossoptosis and a posterior cleft palate. The authors argue that the changes identified (deletions and point mutations) alter site- and stage-specific enhancer function of a neighboring gene, SOX9, which encodes a transcription factor implicated in chondrocyte differentiation and the development of gonads. Loss-of-function mutations in SOX9 result in campomelic dysplasia, a lethal skeletal condition with sex reversal in males2. The observations of Benko et al.1 exemplify the pivotal role of conserved regulatory sequences in development and congenital malformation disorders. Here we add another level of complexity to developmental SOX9 gene regulation by reporting on duplications 5′ of SOX9 that are associated with a phenotype, brachydactyly-anonychia, that is distinct from previously reported SOX9-associated conditions. Our results show that duplications of individual regulatory elements may result in phenotypes that are completely different from those due to mutations within the gene itself.

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Figure 1: Duplications of noncoding elements cause brachydactyly and nail aplasia.

References

  1. Benko, S. et al. Nat. Genet. 41, 359–364 (2009).

    Article  CAS  Google Scholar 

  2. Wagner, T. et al. Cell 79, 1111–1120 (1994).

    Article  CAS  Google Scholar 

  3. Akiyama, H., Chaboissier, M.C., Martin, J.F., Schedl, A. & de Crombrugghe, B. Genes Dev. 16, 2813–2828 (2002).

    Article  CAS  Google Scholar 

  4. Blaydon, D.C. et al. Nat. Genet. 38, 1245–1247 (2006).

    Article  CAS  Google Scholar 

  5. Topol, L., Chen, W., Song, H., Day, T.F. & Yang, Y. J. Biol. Chem. 284, 3323–3333 (2009).

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by a grant from the Deutsche Forschungsgemeinschaft to E.K. and S.M. and by an FFM grant of the Universitätsklinikum Hamburg Eppendorf to I.K.

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Author notes

  1. Ingo Kurth and Eva Klopocki: These authors contributed equally to this work.

  2. S.M. stefan.mundlos@charite.de.

Authors and Affiliations

  1. Institut für Humangenetik, Universitätsklinikum Hamburg Eppendorf, Hamburg, Germany

    Ingo Kurth, Sebastian Vanek & Andreas Gal

  2. Institut für Medizinische Genetik, Charité Universitätsmedizin Berlin, Germany

    Eva Klopocki, Jolieke van Oosterwijk & Stefan Mundlos

  3. Max Planck Institut für Molekulare Genetik, Development & Disease Research Group, Berlin, Germany

    Sigmar Stricker & Stefan Mundlos

  4. Abteilung für Handchirurgie, Berufsgenossenschaftliches Unfallkrankenhaus Hamburg, Hamburg, Germany

    Jens Altmann

  5. Serviço Genética Médica, Faculty of Medicine, Lisbon, Portugal

    Heliosa G Santos

  6. Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands

    Jeske J T van Harssel

  7. Centre for Human Genetics, University Hospitals Leuven, Leuven, Belgium

    Thomy de Ravel

  8. Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK

    Andrew O M Wilkie

Authors
  1. Ingo Kurth
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  2. Eva Klopocki
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  3. Sigmar Stricker
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  4. Jolieke van Oosterwijk
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  7. Heliosa G Santos
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  8. Jeske J T van Harssel
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  9. Thomy de Ravel
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  10. Andrew O M Wilkie
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  11. Andreas Gal
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  12. Stefan Mundlos
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Supplementary Figures 1-2, Supplementary Table 1 and Supplementary Methods (PDF 915 kb)

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Kurth, I., Klopocki, E., Stricker, S. et al. Duplications of noncoding elements 5′ of SOX9 are associated with brachydactyly-anonychia. Nat Genet 41, 862–863 (2009). https://doi.org/10.1038/ng0809-862

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