Dominant Dystrophic Epidermolysis Bullosa (Pasini) Caused by a Novel Glycine Substitution Mutation in the Type VII Collagen Gene (COL7A1)

Jonkman, Marcel F.; Moreno, G.; Rouan, Fatima; Oranje, A.P.; Pulkkinen, Leena; Uitto, Jouni

doi:10.1046/j.1523-1747.1999.00568.x

Cited by 18 publications

(11 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These glycine substitution mutations were previously reported, and, interestingly, the nucleotide changes were identical to those in previous reports (Kon et al 1997;Rouan et al 1998;Jonkman et al 1999;Whittock et al 1999;Lee et al 2000). Glycine residues within the collagenous domain are critical for proper triple helix formation.…”

Section: Resultssupporting

confidence: 87%

Genetic studies of 20 Japanese families of dystrophic epidermolysis bullosa

et al. 2005

View full text Add to dashboard Cite

Dystrophic EB (DEB) is clinically characterized by mucocutaneous blistering in response to minor trauma, followed by scarring and nail dystrophy, and is caused by mutations in the COL7A1 gene encoding type VII collagen. DEB is inherited in either an autosomal dominant (DDEB) or recessive (RDEB) fashion. DDEB basically results from a glycine substitution mutation within the collagenous domain on one COL7A1 allele, while a combination of mutations such as premature stop codon, missense, and splice-site mutations on both alleles causes RDEB. In this study, mutation analysis was performed in 20 distinct Japanese DEB families (16 RDEB and four DDEB). The result demonstrated 30 pathogenic COL7A1 mutations with 16 novel mutations, which included four missense, five nonsense, one deletion, two insertion, one indel, and three splice-site mutations. We confirmed that Japanese COL7A1 mutations were basically family specific, although three mutations, 5818delC, 6573+1G>C, and E2857X, were recurrent based on previous reports. Furthermore, the Q2827X mutation found in two unrelated families would be regarded as a candidate recurrent Japanese COL7A1 mutation. The study furthers our understanding of both the clinical and allelic heterogeneity displayed in Japanese DEB patients.

show abstract

Section: Resultssupporting

confidence: 87%

Genetic studies of 20 Japanese families of dystrophic epidermolysis bullosa

et al. 2005

View full text Add to dashboard Cite

show abstract

“…The G2037E mutation has previously been reported to induce type VII collagen retention in epidermal keratinocytes (Jonkman et al 1999). No transfection study was, however, used to demonstrate the direct relevance of dominant GS mutations to increased intracellular type VII collagen retention, although transfection studies had been performed characterizing the recessive GS G2008R mutation (Chen et al 2002).…”

Section: Discussionmentioning

confidence: 99%

COL7A1 mutation G2037E causes epidermal retention of type VII collagen

et al. 2006

View full text Add to dashboard Cite

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.

show abstract

“…Four micrometer thick cryostat sections were prepared for immunostaining as described previously [21]. Slides were examined at 40x magnification with a Leica DMRA fluorescence microscope (Leica Microsystems GmbH, Wetzlar, Germany).…”

Section: Immunofluorescence Antigen Mappingmentioning

confidence: 99%