ISSN:
1365-2133
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Summary Background There are seven well-known lysosomal storage diseases that produce angiokeratoma corporis diffusum clinically. β-Mannosidosis (MANB1; OMIM248510), first reported in humans in 1986, is a rare hereditary lysosomal storage disease caused by a deficiency of the enzyme β-mannosidase. Since then, 13 cases of β-mannosidase deficiency in ten families have been described. A human β-mannosidase mutation has been reported only by Alkhayat et al. in 1998. Objectives To clarify its pathogenesis we did electron microscopic, biochemical and molecular biological investigations of a Japanese patient with β-mannosidosis. Methods Ultrastructural analyses, enzyme assays, cell culture and mRNA and genomic DNA were sequenced to find mutations in the β-mannosidase gene. 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 β-mannosidase activity. Sequencing the β-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 β-mannosidosis reported in Japan and the second report in which a gene mutation is identified. The biological importance of β-mannose moieties in glycoproteins in basal keratinocytes is suggested.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1365-2133.2003.05365.x
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