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 α-helix domain. We report here on the first inherited missense mutation in WNT10A with associated ectodermal features.
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Acknowledgements
We thank the families and patients that participated in this study. We are also indepted to Lynn Adaimy for providing WNT10A primer sequences. This study was supported by The Swedish Research Council, Swedish Links (Asia), The Indevelops fund, Thuréus fund, Torsten and Ragnar Söderbergs Funds, Uppsala University and the Uppsala University Hospital.
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Nawaz, S., Klar, J., Wajid, M. et al. WNT10A missense mutation associated with a complete Odonto-Onycho-Dermal Dysplasia syndrome. Eur J Hum Genet 17, 1600–1605 (2009). https://doi.org/10.1038/ejhg.2009.81
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DOI: https://doi.org/10.1038/ejhg.2009.81
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