Spectrum of dominant mutations in the desmosomal cadherin desmoglein 1, causing the skin disease striate palmoplantar keratoderma

Item Type:	Article
Title:	Spectrum of dominant mutations in the desmosomal cadherin desmoglein 1, causing the skin disease striate palmoplantar keratoderma
Creators Name:	Hunt, D.M. and Rickman, L. and Whittock, N.V. and Eady, R.A. and Simrak, D. and Dopping-Hepenstal, P.J.C. and Stevens, H.P. and Armstrong, D.K.B. and Hennies, H.C. and Kuster, W. and Hughes, A.E. and Arnemann, J. and Leigh, I.M. and McGrath, J.A. and Kelsell, D.P. and Buxton, R.S.
Abstract:	The adhesive proteins of the desmosome type of cell junction consist of two types of cadherin found exclusively in that structure, the desmogleins and desmocollins, coded by two closely linked loci on human chromosome 18q12.1. Recently we have identified a mutation in the DSG1 gene coding for desmoglein 1 as the cause of the autosomal dominant skin disease striate palmoplantar keratoderma (SPPK) in which affected individuals have marked hyperkeratotic bands on the palms and soles. In the present study we present the complete exon-intron structure of the DSG1 gene, which occupies approximately 43 kb, and intron primers sufficient to amplify all the exons. Using these we have analysed the mutational changes in this gene in five further cases of SPPK. All were heterozygotic mutations in the extracellular domain leading to a truncated protein, due either to an addition or deletion of a single base, or a base change resulting in a stop codon. Three mutations were in exon 9 and one in exon 11, both of which code for part of the third and fourth extracellular domains, and one was in exon 2 coding for part of the prosequence of this processed protein. This latter mutation thus results in the mutant allele synthesising only 25 amino acid residues of the prosequence of the protein so that this is effectively a null mutation implying that dominance in the case of this mutation was caused by haploinsufficiency. The most severe consequences of SPPK mutations are in regions of the body where pressure and abrasion are greatest and where desmosome function is most necessary. SPPK therefore provides a very sensitive measure of desmosomal function.
Keywords:	Cadherin, Desmoglein, Desmosome, Dominance, Epidermis, Keratoderma
Source:	European Journal of Human Genetics
ISSN:	1018-4813
Publisher:	Nature Publishing Group
Volume:	9
Number:	3
Page Range:	197-203
Date:	1 January 2001
Official Publication:	http://www.nature.com/ejhg/journal/v9/n3/abs/5200605a.html
PubMed:	View item in PubMed

Repository Staff Only: item control page