Disease relevance of Epidermolysis Bullosa Dystrophica

• The Hallopeau-Siemens variant of recessive dystrophic epidermolysis bullosa (HS-RDEB) is a severe inherited skin disease characterized by the absence of collagen type VII (COLVII) and anchoring fibrils (AF), caused by mutations in collagen type VII gene (COL7A1) [1].
• Squamous cell carcinoma (SCC) is a common complication in individuals with recessive dystrophic epidermolysis bullosa (RDEB) [2].
• In the recessive dystrophic epidermolysis bullosa patients, transcripts containing in-frame skipping of exon 19 of COL7A1 in the cDNA were detected, and in the junctional epidermolysis bullosa patients transcripts with in-frame skipping of exon 17 of LAMB3 were identified [3].
• Camostat mesylate, a synthetic serine protease inhibitor that is available for the treatment of chronic pancreatitis, demonstrated a striking effect of inhibiting blistering in organ culture of normal human skin with recessive dystrophic epidermolysis bullosa blister fluids [4].
• Management of generalized pruritus in dominant dystrophic epidermolysis bullosa using low-dose oral cyclosporin [5].

High impact information on Epidermolysis Bullosa Dystrophica

• Dystrophic epidermolysis bullosa (DEB) is a family of inherited mechano-bullous disorders caused by mutations in the human type VII collagen gene (COL7A1) [6].
• To determine the efficacy of phenytoin in the treatment of recessive dystrophic epidermolysis bullosa, we performed a randomized, double-blind, placebo-controlled, crossover trial in 36 patients [7].
• Cyclosporin for dystrophic epidermolysis bullosa [8].
• Minocycline for dystrophic epidermolysis bullosa [9].
• In contrast, a positive staining with NC-2 antibodies was observed in the skin of a patient with NC-2 antibodies was observed in the skin of a patient with dystrophic epidermolysis bullosa, who carried a 14-bp deletion at one of the intro-exon junctions of the collagen VII gene [10].

Chemical compound and disease context of Epidermolysis Bullosa Dystrophica

• A generated methionine to lysine substitution, M2798K, that is associated with recessive dystrophic epidermolysis bullosa, was unable to form antiparallel dimers [11].
• A glycine-to-arginine substitution in the triple-helical domain of type VII collagen in a family with dominant dystrophic epidermolysis bullosa pruriginosa [12].
• The staining patterns for nidogen and heparan sulfate proteoglycan were examined in 11 patients with either junctional, dominant dystrophic, or recessive dystrophic epidermolysis bullosa, and were found to be not different from the patterns observed in normal skin [13].
• Subsequently we administered camostat mesylate by topical application to four patients with recessive dystrophic epidermolysis bullosa to assess its ability to reduce blistering [4].
• These findings actually supported the hypothesis that a kind of serine protease had a close relationship with blistering in recessive dystrophic epidermolysis bullosa and that therapy with a clinically usable protease inhibitor was useful for the treatment of this disease [4].

Biological context of Epidermolysis Bullosa Dystrophica

• Genetic linkage of type VII collagen (COL7A1) to dominant dystrophic epidermolysis bullosa in families with abnormal anchoring fibrils [14].
• Deletions within COL7A1 exons distant from consensus splice sites alter splicing and produce shortened polypeptides in dominant dystrophic epidermolysis bullosa [15].
• Human type VII collagen: genetic linkage of the gene (COL7A1) on chromosome 3 to dominant dystrophic epidermolysis bullosa [16].
• Modulation of disease severity of dystrophic epidermolysis bullosa by a splice site mutation in combination with a missense mutation in the COL7A1 gene [17].
• Targeted inactivation of the type VII collagen gene (Col7a1) in mice results in severe blistering phenotype: a model for recessive dystrophic epidermolysis bullosa [18].

Anatomical context of Epidermolysis Bullosa Dystrophica

• Constitutive activation of the collagenase promoter in recessive dystrophic epidermolysis bullosa fibroblasts: role of endogenously activated AP-1 [19].
• Mutations in the gene COL7A1 encoding type VII collagen cause dystrophic epidermolysis bullosa, a clinically heterogeneous autosomal dominant or recessive blistering disorder of the skin and mucous membranes [20].
• A similar pattern has been seen in keratinocytes from patients with recessive dystrophic epidermolysis bullosa (RDEB), in whom the incidence of cutaneous SCC is markedly increased [21].
• Toenail dystrophy with COL7A1 glycine substitution mutations segregates as an autosomal dominant trait in 2 families with dystrophic epidermolysis bullosa [22].
• This case lends further support to an association between autosomal recessive generalized dystrophic epidermolysis bullosa and increased levels of alpha-fetoprotein, positive amniotic fluid acetylcholinesterase, and normal ultrasound findings [23].

Gene context of Epidermolysis Bullosa Dystrophica

• So we can suspect that recessive dystrophic epidermolysis bullosa phenotypic variability could be related to patients' collagenase activity heterogeneity, linked to imbalance between MMP-1 and TIMP-1 [24].
• Collagenase and stromelysin activities have been found to be overexpressed in skin cultures of some recessive dystrophic epidermolysis bullosa patients, and tissue destruction in the disease process might result from an imbalance of metalloproteinases (MMP) over tissueinhibitor of metalloproteinases (TIMP) [24].
• Characterization of 18 new mutations in COL7A1 in recessive dystrophic epidermolysis bullosa provides evidence for distinct molecular mechanisms underlying defective anchoring fibril formation [25].
• Disruption of ERBB2IP is not associated with dystrophic epidermolysis bullosa in both father and son carrying a balanced 5;13 translocation [26].
• Reduced expression of insulin-like growth factor-binding protein-3 (IGFBP-3) in Squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa [2].

Analytical, diagnostic and therapeutic context of Epidermolysis Bullosa Dystrophica

• Use of type VII collagen gene (COL7A1) markers in prenatal diagnosis of recessive dystrophic epidermolysis bullosa [27].
• In this study, we searched for mutations in dominant dystrophic epidermolysis bullosa using polymerase chain reaction amplification of segments of COL7A1, followed by heteroduplex analysis [28].
• Prenatal diagnosis of dominant and recessive dystrophic epidermolysis bullosa: application and limitations in the use of KF-1 and LH 7:2 monoclonal antibodies and immunofluorescence mapping technique [29].
• In this study we examined the inhibitory effect of clinically usable serine protease inhibitors for blister formation in organ culture and in clinical trials of recessive dystrophic epidermolysis bullosa patients [4].

References