Genotype-phenotype correlation in skin fragility-ectodermal dysplasia syndrome resulting from mutations in plakophilin 1

T Hamada, A P South, Y Mitsuhashi, T Kinebuchi, O Bleck, G H S Ashton, Y Hozumi, T Suzuki, T Hashimoto, R A J Eady, J A McGrath

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

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 I I donor splice site mutation in the plakophilin I gone, 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 (similar to8%) 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 I 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 I (OMIM 604536). This new 'mitis' phenotype provides further clinicopathological evidence for the role of plakophilin I in keratinocyte cell-cell adhesion and ectodermal development.
Original languageEnglish
Pages (from-to)107 - 114
Number of pages8
JournalExperimental Dermatology
Volume11
Issue number2
DOIs
Publication statusPublished - Apr 2002

Fingerprint

Dive into the research topics of 'Genotype-phenotype correlation in skin fragility-ectodermal dysplasia syndrome resulting from mutations in plakophilin 1'. Together they form a unique fingerprint.

Cite this