title: Genomic amplification of the human plakophilin 1 gene and detection of a new mutation in ectodermal dysplasia/skin fragility syndrome.
abstract: Ectodermal dysplasia/skin fragility syndrome is a recently described autosomal recessive disease affecting skin, nails, and hair (MIM 604536), that results 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 polymerase chain reaction-based mutation screening. Using polymerase chain reaction amplification of genomic DNA, we identified 15 exons spanning approximately 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 comprised skin erosions, dystrophic nails, sparse hair, and painful thickening and cracking of palms and soles. Skin biopsy showed negative immunolabeling with 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 differentiating keratinocytes.
authors.affiliation: Department of Cell and Molecular Pathology, St John's Institute of Dermatology, The Guy's, King's College, and St Thomas' Hospitals' Medical School, St Thomas' Hospital, London, U.K. neil.2.whittock@kcl.ac.uk
authors.forename: N V
authors.initials: NV
authors.lastname: Whittock
authors.forename: M
authors.initials: M
authors.lastname: Haftek
authors.forename: N
authors.initials: N
authors.lastname: Angoulvant
authors.forename: F
authors.initials: F
authors.lastname: Wolf
authors.forename: H
authors.initials: H
authors.lastname: Perrot
authors.forename: R A
authors.initials: RA
authors.lastname: Eady
authors.forename: J A
authors.initials: JA
authors.lastname: McGrath
mesh_terms: D000293:Adolescent; D004274:DNA, Recombinant; D003896:Desmosomes; D004476:Ectodermal Dysplasia / Q000235:genetics*; D005784:Gene Amplification; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009154:Mutation; D051191:Plakophilins; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D013194:Staining and Labeling
chemical_list: D004274:DNA, Recombinant; C495335:PKP1 protein, human; D051191:Plakophilins; D011506:Proteins