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Genotype–phenotype correlation in skin fragility‐ectodermal dysplasia syndrome resulting from mutations in plakophilin 1
Author(s) -
Hamada T.,
South A. P.,
Mitsuhashi Y.,
Kinebuchi T.,
Bleck O.,
Ashton G. H. S.,
Hozumi Y.,
Suzuki T.,
Hashimoto T.,
Eady R. A. J.,
McGrath J. A.
Publication year - 2002
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1034/j.1600-0625.2002.110202.x
Subject(s) - genodermatosis , palmoplantar keratoderma , desmosome , skin biopsy , pathology , ectodermal dysplasia , biology , phenotype , medicine , dermatology , biopsy , genetics , hyperkeratosis , gene , cell
We report a 42‐year‐old Japanese man with an unusual autosomal recessive genodermatosis. The clinical features comprised normal skin at birth, loss of scalp hair at 3‐months of age after a febrile illness, progressive nail dystrophy during infancy, palmoplantar keratoderma starting around the age of 18 years and trauma‐induced skin fragility and blisters noted from the age of 20 years. Skin biopsy of rubbed non‐lesional skin revealed widening of spaces between adjacent keratinocytes from the suprabasal layer upwards. Electron microscopy demonstrated a reduced number of hypoplastic desmosomes. Immunohistochemical labeling showed a reduction in intercellular staining for the desmosome component plakophilin 1. Mutation analysis revealed a homozygous intron 11 donor splice site mutation in the plakophilin 1 gene, 2021+1 G>A (GenBank no. Z34974). RT‐PCR, using RNA extracted from the skin biopsy, provided evidence for residual low levels of the full‐length wild‐type transcript (∼8%) as well as multiple other near full‐length transcripts, one of which was in frame leading to deletion of 17 amino acids from the 9th arm‐repeat unit of the plakophilin 1 tail domain. Thus, the molecular findings help explain the clinical features in the patient, who has a similar but milder phenotype to previously reported patients with skin fragility‐ectodermal dysplasia syndrome associated with complete ablation of plakophilin 1 (OMIM 604536). This new ‘mitis’ phenotype provides further clinicopathological evidence for the role of plakophilin 1 in keratinocyte cell–cell adhesion and ectodermal development.