TY - JOUR
T1 - Genotype-phenotype correlation in skin fragility-ectodermal dysplasia syndrome resulting from mutations in plakophilin 1
AU - Hamada, T
AU - South, A P
AU - Mitsuhashi, Y
AU - Kinebuchi, T
AU - Bleck, O
AU - Ashton, G H S
AU - Hozumi, Y
AU - Suzuki, T
AU - Hashimoto, T
AU - Eady, R A J
AU - McGrath, J A
PY - 2002/4
Y1 - 2002/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0036548393&partnerID=8YFLogxK
U2 - 10.1034/j.1600-0625.2002.110202.x
DO - 10.1034/j.1600-0625.2002.110202.x
M3 - Article
VL - 11
SP - 107
EP - 114
JO - Experimental Dermatology
JF - Experimental Dermatology
IS - 2
ER -