Genomic amplification of the human plakophilin 1 gene and detection of a new mutation in ectodermal dysplasia/skin fragility syndrome

Ectodermal dysplasia/skin fragility syndrome is a recently described autoso mal recessive disease affecting skin, nails, and hair (MIM 604536), that re sults from mutations in plakophilin 1, a structural component of desmosomes , We report a new plakophilin 1 mutation in an affected patient as well as detailing the intron-exon organization of the gene to facilitate future pol ymerase chain reaction-based mutation screening. Using polymerase chain rea ction amplification of genomic DNA, we identified 15 exons spanning approxi mately 50 kb, Direct sequencing disclosed several nonpathogenic intragenic polymorphisms, as well as a homozygous splice site mutation (1233-2 A-->T; GenBank Z73678) in a 17 y old affected male. The clinical features comprise d skin erosions, dystrophic nails, sparse hair, and painful thickening and cracking of palms and soles. Skin biopsy showed negative immunolabeling wit h an anti-plakophilin 1 antibody and small desmosomes, These results expand the database of plakophilin 1 mutations and demonstrate the importance of this protein in the stabilization of desmosomal adhesion in terminally diff erentiating keratinocytes.