Conflicts of interest None declared.
Novel truncating mutations in PKP1 and DSP cause similar skin phenotypes in two Brazilian families
Article first published online: 21 OCT 2008
© 2008 The Authors. Journal Compilation © 2008 British Association of Dermatologists
British Journal of Dermatology
Volume 160, Issue 3, pages 692–697, March 2009
How to Cite
Tanaka, A., Lai-Cheong, J.E., Café, M.E.M., Gontijo, B., Salomão, P.R., Pereira, L. and McGrath, J.A. (2009), Novel truncating mutations in PKP1 and DSP cause similar skin phenotypes in two Brazilian families. British Journal of Dermatology, 160: 692–697. doi: 10.1111/j.1365-2133.2008.08900.x
- Issue published online: 17 FEB 2009
- Article first published online: 21 OCT 2008
- Accepted for publication 4 August 2008
- ectodermal dysplasia;
- skin fragility
Inherited mutations in components of desmosomes result in a spectrum of syndromes characterized by variable abnormalities in the skin and its appendages, including blisters and erosions, palmoplantar hyperkeratosis, woolly hair or hypotrichosis and, in some cases, extracutaneous features such as cardiomyopathy. We investigated the molecular basis of two Brazilian patients presenting with clinical features consistent with ectodermal dysplasia-skin fragility syndrome. In patient 1 we identified a homozygous nonsense mutation, p.R672X, in the PKP1 gene (encoding plakophilin 1). This particular mutation has not been reported previously but is similar to the molecular pathology underlying other cases of this syndrome. In patient 2 we found compound heterozygosity for two frameshift mutations, c.2516del4 and c.3971del4, in the DSP gene (encoding desmoplakin). Although there was considerable clinical overlap in the skin and hair abnormalities in these two cases, patient 2 also had early-onset cardiomyopathy. The mutation c.3971del4 occurs in the longer desmoplakin-I isoform (which is the major cardiac transcript) but not in the more ubiquitous desmoplakin-II. In contrast, PKP1 is not expressed in the heart, which accounts for the lack of cardiomyopathy in patient 1. Collectively, these cases represent the first desmosomal genodermatoses to be reported from Brazil and add to genotype–phenotype correlation in this group of inherited disorders. Loss-of-function mutations in the DSP gene can result in a phenotype similar to ectodermal dysplasia-skin fragility syndrome resulting from PKP1 mutations but only DSP pathology is associated with cardiac disease.