COL7A1 mutation G2037E causes epidermal retention of type VII collagen.
COL7A1 glycine substitution (GS) mutations result in dominant and recessive dystrophic epidermolysis bullosa (DDEB and RDEB). Here, we report a DDEB family in which retention of type VII collagen by epidermal keratinocytes was observed for a female proband. Mutational analysis detected a GS mutation, G2037E, in the proband and her affected father. To demonstrate direct association of G2037E and type VII collagen retention we 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. The increase in type VII collagen cytoplasmic staining in the G2037E/wild transfectant cell samples was compared with that for control/wild-type cells. Intracellular collagen VII staining in the G2037E (alone)-transfected cells was even stronger than for the G2037E/wild transfection sample. These results indicate 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 have more severe phenotypes than heterozygotes. This study furthers our understanding of GS COL7A1 mutations in DEB.
Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, 060-8638, Sapporo, Japan. smartdai@med.hokudai.ac.jp.
Daisuke
D
Sawamura
Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, 060-8638, Sapporo, Japan.
Kazuko
K
Sato-Matsumura
Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Satoko
S
Shibata
Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Akari
A
Tashiro
Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Masutaka
M
Furue
Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, 060-8638, Sapporo, Japan.
Maki
M
Goto
Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, 060-8638, Sapporo, Japan.
Kaori
K
Sakai
Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, 060-8638, Sapporo, Japan.
Masashi
M
Akiyama
Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, 060-8638, Sapporo, Japan.
Hideki
H
Nakamura
Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, 060-8638, Sapporo, Japan.
Hiroshi
H
Shimizu
D024143:Collagen Type VII / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D016108:Epidermolysis Bullosa Dystrophica / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D014162:Transfection
D024143:Collagen Type VII