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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 volume 38, pages 1245–1247 (2006)Cite this article

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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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Figure 1: RSPO4 mutations in inherited anonychia.
Figure 2: Whole-mount in situ hybridization of E15.5 mouse embryos showing specific expression of Rspo4 at the sites of nail development.

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.

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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.).

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Author notes

  1. Diana C Blaydon and Yoshiyuki Ishii: These authors contributed equally to this work.

Authors and Affiliations

  1. Centre for Cutaneous Research, Institute of Cell & Molecular Science, Queen Mary's School of Medicine and Dentistry, Queen Mary, University of London, London, E1 4AT, Whitechapel, 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, 10032, New York, 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, Berlin, D-13092, Germany

    Franz Rüschendorf

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

Authors
  1. Diana C Blaydon
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  2. Yoshiyuki Ishii
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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.

Corresponding author

Correspondence to David P Kelsell.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Two pedigrees (P1 and F) with genotypes of microsatellite/SNPs mapping to 20p13. (PDF 103 kb)

Supplementary Fig. 2

Pedigree P2 with genotype data. (PDF 168 kb)

Supplementary Fig. 3

Haplotypes of family P2 and schematic showing minimal region harboring the anonychia gene. (PDF 108 kb)

Supplementary Fig. 4

Examples of two mutations detected in the anonychia families. (PDF 54 kb)

Supplementary Table 1

Primers for additional microsatellite markers between D20S117 and D20S906 and for mutation analysis of genes in the candidate region. (PDF 124 kb)

Supplementary Methods (PDF 83 kb)

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Blaydon, D., Ishii, Y., O'Toole, E. et al. The gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, is mutated in inherited anonychia. Nat Genet 38, 1245–1247 (2006). https://doi.org/10.1038/ng1883

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