Abstract | BACKGROUND: OBJECTIVES: To clarify its pathogenesis we did electron microscopic, biochemical and molecular biological investigations of a Japanese patient with beta-mannosidosis. METHODS: RESULTS: Electron microscopy of skin biopsy specimens from the patient showed cytoplasmic vacuolation of lysosomes in blood and lymph vessels, endothelial cells, fibroblasts, secretory portions of eccrine sweat glands, neural cells and basal keratinocytes in the epidermis. This vacuolation was also observed in cultured keratinocytes and fibroblasts. Assays of seven enzyme activities in plasma and cultured skin fibroblasts showed a marked decrease of beta-mannosidase activity. Sequencing the beta-mannosidase cDNA revealed a four-base ( ATAA) insertion between exons 7 and 8, resulting in a frameshift at codon 321 and termination at codon 325. Analysis of the patient's genomic DNA revealed a novel homozygous A(+1)-->G splice site mutation in intron 7. CONCLUSIONS: To our knowledge, this is the first case of beta-mannosidosis reported in Japan and the second report in which a gene mutation is identified. The biological importance of beta- mannose moieties in glycoproteins in basal keratinocytes is suggested.
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Authors | Y Uchino, T Fukushige, S Yotsumoto, T Hashiguchi, H Taguchi, N Suzuki, I Konohana, T Kanzaki |
Journal | The British journal of dermatology
(Br J Dermatol)
Vol. 149
Issue 1
Pg. 23-9
(Jul 2003)
ISSN: 0007-0963 [Print] England |
PMID | 12890191
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA, Complementary
- Mannosidases
- beta-Mannosidase
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Topics |
- Cells, Cultured
- DNA Mutational Analysis
- DNA, Complementary
(genetics)
- Female
- Humans
- Keratosis
(genetics, pathology)
- Male
- Mannosidases
(blood, deficiency, genetics)
- Microscopy, Electron
- Middle Aged
- Point Mutation
- Reverse Transcriptase Polymerase Chain Reaction
- Skin
(ultrastructure)
- alpha-Mannosidosis
(genetics, pathology)
- beta-Mannosidase
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