WNT10A missense mutation associated with a complete odonto-onycho-dermal dysplasia syndrome

Eur J Hum Genet. 2009 Dec;17(12):1600-5. doi: 10.1038/ejhg.2009.81. Epub 2009 May 27.

Abstract

Wnt signalling is one of a few pathways that are crucial for controlling genetic programs during embryonic development as well as in adult tissues. WNT10A is expressed in the skin and epidermis and it has shown to be critical for the development of ectodermal appendages. A nonsense mutation in WNT10A was recently identified in odonto-onycho-dermal dysplasia (OODD; MIM 257980), a rare syndrome characterised by severe hypodontia, nail dystrophy, smooth tongue, dry skin, keratoderma and hyperhydrosis of palms and soles. We identified a large consanguineous Pakistani pedigree comprising six individuals affected by a complete OODD syndrome. Autozygosity mapping using SNP array analysis showed that the affected individuals are homozygous for the WNT10A gene region. Subsequent mutation screening showed a homozygous c.392C>T transition in exon 3 of WNT10A, which predicts a p.A131V substitution in a conserved alpha-helix domain. We report here on the first inherited missense mutation in WNT10A with associated ectodermal features.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Amino Acid Sequence
  • Base Sequence
  • Ectodermal Dysplasia / complications*
  • Ectodermal Dysplasia / genetics*
  • Family
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation, Missense / genetics*
  • Pedigree
  • Protein Structure, Secondary
  • Syndrome
  • Wnt Proteins / chemistry
  • Wnt Proteins / genetics*

Substances

  • WNT10A protein, human
  • Wnt Proteins