Mutations in WNT10A lead to the odonto-onycho-dermal dysplasia syndrome – the first Australian case

  • Dr Philip Tong, Department of Dermatology, St George Hospital, University of New South Wales, Sydney, Australia, Australia
  • Dr Michel van Geel, Department of Dermatology, Maastricht University Medical Center, Maastricht, The Netherlands, The Netherlands
  • Dr Michael Gattas, Department of Paediatrics and Child Health, University of Queensland, Brisbane, Queensland, Australia, Australia
  • Dr Yvo Kesler, Department of Dermatology, Maastricht University Medical Center, Maastricht, The Netherlands, The Netherlands
  • Dr Kim Tran, Department of Dermatology, St George Hospital, University of New South Wales, Sydney, Australia, Australia
  • Professor Peter Steijlen, Department of Dermatology, Maastricht University Medical Center, Maastricht, The Netherlands, The Netherlands
  • Professor Dedee Murrell, Department of Dermatology, St George Hospital, University of New South Wales, Sydney, Australia, Australia
  • Dr Maurice van Steensel, Department of Dermatology, Maastricht University Medical Center, Maastricht, The Netherlands, The Netherlands

Introduction: Odonto-onycho-dermal dysplasia (OODD) is a rare autosomal recessive ectodermal dysplasia characterised by hypodontia, hyponychia, and palmoplantar keratoderma. We present a Caucasian man of northern European descent with a novel nonsense mutation in WNT10A and propose phenotypic variability is seen in this condition associated with the same genetic mutation.
Methods: This man presented with hypodontia, sparse scalp hair, facial milia, erythematous dry skin and thin nails, palmoplantar keratoderma and hyperhydrosis. The differential diagnosis included X-linked hypohidrotic ectodermal dysplasia and odonto-onycho-dermal dysplasia. The WNT10A gene was sequenced. Skin biopsies from facial milia, inner upper left arm and left palm for routine histology and immunohistochemistry (IHC) with anti-human WNT10A polyclonal rabbit antibody.
Results: We found compound heterozygous nonsense mutations in the WNT10A gene: c.321C>A (p.Cys107Stop) and c.328C>T (p.Arg128Stop). The epidermal architecture was intact with irregular differentiation in places and a thin corneal layer. Structural differences were seen in the hair follicles when compared to control specimens. IHC staining of control skin revealed clear punctuate staining of the epidermis and was more pronounced in adnexal structures. Staining in patient samples, was reduced when compared to controls. It was not possible to amplify WNT10A by PCR from cDNA from skin biopsies.
Conclusion: Patients with OODD appear to have one common mutation in c.321C>A and our data supports the evidence for phenotypic heterogeneity associated with mutations in WNT10A. The expression of WNT10A we observed is consistent with clinical features of OODD and supported by IHC studies suggesting loss of function of the resulting truncated protein.