COL7A1 mutation G2037E causes epidermal retention of type VII collagen

概要

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COL7A1 glycine substitution (GS) mutations result in dominant and recessive dystrophic epidermolysis bullosa (DDEB and RDEB). Here, we report a DDEB family in which a female proband showed retention of type VII collagen inepidermal keratinocytes. Mutational analysis detected a GS mutation; G2037E in the proband and her affected father. To demonstrate the direct association of G2037E and type VII collagen retention, we have introduced this mutated COL7A1 gene into cultured keratinocytes using retroviral methods. This mutation was dominant, so we transferred a 1:1 mixture of wild type (unaffected) and G2037E mutated COL7A1 together, in addition to the unaffected gene or the mutated gene alone. An increase in type VII collagen cytoplasmic staining in the G2037E/wild transfectant cell samples compared with the control/wild type cells. The G2037E (alone) transfected cells showed even stronger intracellular collagen VII staining than the G2037E/wild transfection sample. These results demonstrate that the G2037E COL7A1 mutation leads to increased epidermal retention of type VII collagen in vivo, and also suggests that homozygotes carrying this dominant GS mutation may show more severe phenotypes than heterozygotes. This study furthers our understanding of GS COL7A1 mutations in DEB.
2006-05-01