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Deficiency of PORCN, a regulator of Wnt signaling, is associated with focal dermal hypoplasia

Abstract

Focal dermal hypoplasia (FDH) is an X-linked dominant multisystem birth defect affecting tissues of ectodermal and mesodermal origin. Using a stepwise approach of (i) genetic mapping of FDH, (ii) high-resolution comparative genome hybridization to seek deletions in candidate chromosome areas and (iii) point mutation analysis in candidate genes, we identified PORCN, encoding a putative O-acyltransferase and potentially crucial for cellular export of Wnt signaling proteins, as the gene mutated in FDH. The findings implicate FDH as a developmental disorder caused by a deficiency in PORCN.

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Figure 1: Zooming in on mutations associated with FDH.

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References

  1. Gorlin, R.J., Cohen, M.M.J. & Hennekam, R.C.M. in Oxford Monographs on Medical Genetics Vol. 42 571–576 (Oxford Univ. Press, Oxford, 2001).

    Google Scholar 

  2. Selzer, R.R. et al. Genes Chromosom. Cancer 44, 305–319 (2005).

    Article  CAS  Google Scholar 

  3. Caricasole, A., Ferraro, T., Rimland, J.M. & Terstappen, G.C. Gene 288, 147–157 (2002).

    Article  CAS  Google Scholar 

  4. Willert, K. et al. Nature 423, 448–452 (2003).

    Article  CAS  Google Scholar 

  5. He, X. & Axelrod, J.D.A. Development 133, 2597–2603 (2006).

    Article  CAS  Google Scholar 

  6. Clevers, H. Cell 127, 469–480 (2006).

    Article  CAS  Google Scholar 

  7. Moon, R.T., Kohn, A.D., De Ferrari, G.V. & Kaykas, A. Nat. Rev. Genet. 5, 691–701 (2004).

    Article  CAS  Google Scholar 

  8. Freude, K. et al. Am. J. Hum. Genet. 75, 305–309 (2004).

    Article  CAS  Google Scholar 

  9. Derry, J.M. et al. Nat. Genet. 22, 286–290 (1999).

    Article  CAS  Google Scholar 

  10. Puck, J.M. & Willard, H.F. N. Engl. J. Med. 338, 325–328 (1998).

    Article  CAS  Google Scholar 

  11. Happle, R. & Lenz, W. Br. J. Dermatol. 96, 133–135 (1977).

    Article  CAS  Google Scholar 

  12. Gordon, M.D. & Nusse, R. J. Biol. Chem. 281, 22429–22433 (2006).

    Article  CAS  Google Scholar 

  13. Tanaka, K., Okabayashi, K., Asashima, M., Perrimon, N. & Kadowaki, T. Eur. J. Biochem. 267, 4300–4311 (2000).

    Article  CAS  Google Scholar 

  14. Hancock, S. et al. Am. J. Med. Genet. 110, 370–379 (2002).

    Article  Google Scholar 

  15. Behninger, C. & Rott, H.D. Genet. Couns. 11, 157–167 (2000).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to the affected individuals and their families for their cooperation, and we thank M. Schad (Deutsches Ressourcenzentrum für Genomforschung, Berlin) for help with inverted graphical presentation of CGH data. This research was supported by BMBF (Netzwerk für Ichthyosen und verwandte Verhornungsstörungen (NIRK)), the European Union (Coordination Action GeneSkin) and Forschungspool des Fachbereichs Medizin der Philipps-Universität Marburg.

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Authors and Affiliations

Authors

Contributions

This study was designed by K.-H.G. and R.H. Clinical phenotype assessment and proband recruitment were performed by A.K, M.d.C.B., H.E., U.G., M.H., K.H., V.O., M.P., C.S., Z.S., G.T., H.T. and R.H.; genetic mapping, mutation analyses and X inactivation analysis were performed by D.B., B.F. and F.O.; data analysis was performed by K.-H.G., D.B and F.O. and K.-H.G., F.O., A.K. and R.H. contributed to the writing of the paper.

Corresponding author

Correspondence to Karl-Heinz Grzeschik.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Developmental defects associated with FDH. (PDF 668 kb)

Supplementary Fig. 2

MAPH analysis of PORCN in FDH patients GG1, GG2 and GG11. (PDF 651 kb)

Supplementary Fig. 3

Genomic sequences of FDH patients GG3–GG10, encompassing mutations in the PORCN gene, and corresponding wild-type sequences. (PDF 979 kb)

Supplementary Table 1

Two-point linkage analysis for FDH and 15 X-chromosomal markers in family Tu1. (PDF 95 kb)

Supplementary Table 2

Primer pairs and conditions used in PORCN analysis. (PDF 83 kb)

Supplementary Methods (PDF 110 kb)

Supplementary Note (PDF 96 kb)

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Grzeschik, KH., Bornholdt, D., Oeffner, F. et al. Deficiency of PORCN, a regulator of Wnt signaling, is associated with focal dermal hypoplasia. Nat Genet 39, 833–835 (2007). https://doi.org/10.1038/ng2052

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