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 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.
Whittock
N V
NV
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
Haftek
M
M
Angoulvant
N
N
Wolf
F
F
Perrot
H
H
Eady
R A
RA
McGrath
J A
JA
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
D004274:DNA, Recombinant; C495335:PKP1 protein, human; D051191:Plakophilins; D011506:Proteins