Diffuse nonepidermolytic palmoplantar keratoderma caused by a recurrent nonsense mutation in DSG1.
BACKGROUND
Mutations in genes coding for 2 desmosomal proteins, desmoglein 1 and desmoplakin, have been shown to cause autosomal dominant keratoderma palmoplantaris striata.


METHODS
We describe a family affected with a diffuse nonstriated form of palmoplantar keratoderma. Histopathologic examination of skin biopsy specimens disclosed cell-cell disadhesion in the suprabasal layers of the epidermis, as previously described in keratoderma palmoplantaris striata. We therefore genotyped all family members using microsatellite markers encompassing 3 keratoderma palmoplantaris striata-associated loci. Haplotype analysis suggested linkage of the disease to 18q12.1, which harbors the DSG1 gene, encoding desmoglein 1. Mutation analysis eventually led to the identification of a causative recurrent nonsense mutation in this gene.


CONCLUSIONS
Mutations in DSG1 are not exclusively associated with striated palmoplantar keratoderma. The present study illustrates the efficacy of an integrative diagnostic approach to palmoplantar keratodermas involving clinical assessment, pathologic examination, microsatellite marker screening, and mutational analysis.
Keren
Hannah
H
Department of Dermatology and Laboratory of Molecular Dermatology, Rambam Medical Center, Haifa, Israel.
Bergman
Reuven
R
Mizrachi
Mordechai
M
Kashi
Yechiezkel
Y
Sprecher
Eli
E
D001120:Arginine; D015820:Cadherins / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D018389:Codon, Nonsense; D018388:Codon, Terminator; D003596:Cytosine; D051183:Desmoglein 1; D005799:Genes, Dominant; D008040:Genetic Linkage; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D007645:Keratoderma, Palmoplantar / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D013941:Thymine
D015820:Cadherins; D018389:Codon, Nonsense; D018388:Codon, Terminator; D051183:Desmoglein 1; D003596:Cytosine; D001120:Arginine; D013941:Thymine