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The gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, is mutated in inherited anonychia

Nature Genetics 38, 1245–1247 (2006) | Download Citation

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Abstract

Anonychia and hyponychia congenita (OMIM 206800) are rare autosomal recessive conditions in which the only presenting phenotype is the absence or severe hypoplasia of all fingernails and toenails. After determining linkage to chromosome 20p13, we identified homozygous or compound heterozygous mutations in the gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, in eight affected families. Rspo4 expression was specifically localized to developing mouse nail mesenchyme at embryonic day 15.5, suggesting a crucial role in nail morphogenesis.

NOTE: In the version of this article initially published, the national origin of the three consanguineous families (P2–P4) was incorrectly described as Indian. The national origin of all three families (P2–P4) is Pakistani. This error has been corrected in the HTML and PDF versions of the article.

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Change history

  • 27 November 2006

    In the version of this article initially published, the national origin of the three consanguineous families (P2–P4) was incorrectly described as Indian. The national origin of all three families (P2–P4) is Pakistani. This error has been corrected in the HTML and PDF versions of the article.

References

  1. 1.

    , & in Diseases of the Nails and Their Management (Blackwell Science, Oxford, 2001).

  2. 2.

    , , & J. Invest. Dermatol. 107, 639–646 (1996).

  3. 3.

    et al. Nat. Genet. 19, 47–50 (1998).

  4. 4.

    et al. Nat. Genet. 19, 51–55 (1998).

  5. 5.

    et al. Am. J. Hum. Genet. 69, 67–74 (2001).

  6. 6.

    et al. Nature 382, 360–363 (1996).

  7. 7.

    & Arch. Dermatol. 107, 752–753 (1973).

  8. 8.

    et al. Hum. Genet. 118, 708–715 (2006).

  9. 9.

    , , & Nat. Genet. 25, 12–13 (2000).

  10. 10.

    et al. Biochim. Biophys. Acta 1676, 51–62 (2004).

  11. 11.

    , , , & J. Biol. Chem. 281, 13247–13257 (2006).

  12. 12.

    et al. Cell Cycle 5, 23–26 (2006).

  13. 13.

    et al. Dev. Cell 7, 525–534 (2004).

  14. 14.

    In Situ Hybridization: a Practical Approach. (Oxford Univ. Press, New York, 1992).

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Acknowledgements

We thank the family members for their participation in this study, and we would like to acknowledge the assistance of K. Fantauzzo and H. Bazzi from the Department of Genetics and Development, Columbia University. This work was partially supported by the Association for International Cancer Research (D.P.K.), the German Federal Ministry of Science and Education through the National Genome Research Network (F.R.), the Ministry of Education, Culture, Sports, Science and Technology in Japan (Y.I.) and the National Institutes of Health/US Public Health Service grant R01AR44924 (A.M.C.).

Author information

    • Diana C Blaydon
    •  & Yoshiyuki Ishii

    These authors contributed equally to this work.

Affiliations

  1. Centre for Cutaneous Research, Institute of Cell & Molecular Science, Queen Mary's School of Medicine and Dentistry, Queen Mary, University of London, Whitechapel, London E1 4AT, UK.

    • Diana C Blaydon
    • , Edel A O'Toole
    • , Harriet C Unsworth
    • , Muy-Teck Teh
    • , Claire Sinclair
    •  & David P Kelsell

  2. Department of Dermatology and Genetics and Department of Development, Columbia University College of Physicians & Surgeons, 630 West 168th Street, New York, New York 10032, USA.

    • Yoshiyuki Ishii
    • , Muhammad Wajid
    •  & Angela M Christiano

  3. Department of Functional Genetics and Genomics, Max Delbrück Center for Molecular Medicine, Robert Rössle Str. 10, D-13092 Berlin, Germany.

    • Franz Rüschendorf

  4. Department of Dermatology, University Central Hospital, 20520 Turku 52, Finland.

    • Väinö K Hopsu-Havu

  5. Cancer Research UK, 44 Lincolns Inn Fields, London WC2A 3PX, UK.

    • Nicholas Tidman

  6. Birmingham Children's Hospital, Steelhouse Lane, Birmingham B4 6NH, UK.

    • Celia Moss

  7. Department of Paediatric Dermatology, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland.

    • Rosemarie Watson

  8. Bristol Dermatology Centre, Bristol Royal Infirmary, Bristol BS2 8HW, UK.

    • David de Berker

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Contributions

The molecular study was designed and supervised by D.P.K. and A.M.C. The clinical study was designed and supervised by E.A.O.T. Laboratory work was performed by D.C.B., Y.I., H.C.U., M.-T.T. and C.S.; statistical analysis was performed by F.R.; clinical contributions were made by V.K.H., N.T., C.M., R.W., D.d.B. and M.W. D.C.B., Y.I., E.A.O.T., F.R., A.M.C. and D.P.K. all contributed to the writing of the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to David P Kelsell.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    Two pedigrees (P1 and F) with genotypes of microsatellite/SNPs mapping to 20p13.

  2. 2.

    Supplementary Fig. 2

    Pedigree P2 with genotype data.

  3. 3.

    Supplementary Fig. 3

    Haplotypes of family P2 and schematic showing minimal region harboring the anonychia gene.

  4. 4.

    Supplementary Fig. 4

    Examples of two mutations detected in the anonychia families.

  5. 5.

    Supplementary Table 1

    Primers for additional microsatellite markers between D20S117 and D20S906 and for mutation analysis of genes in the candidate region.

  6. 6.

    Supplementary Methods

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DOI

https://doi.org/10.1038/ng1883

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