A missense mutation in type VII collagen in two affected siblings with recessive dystrophic epidermolysis bullosa

Christiano, Angela M.; Greenspan, Daniel S.; Hoffman, Guy G.; Zhang, Xin; Tamai, Yoshiko; Lin, Andrew N.; Dietz, Harry C.; Hovnanian, Alain; Uitto, Jouni

doi:10.1038/ng0593-62

Cited by 184 publications

(116 citation statements)

References 32 publications

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“…Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited skin blistering disease caused exclusively by mutations in the gene-encoding type VII collagen, COL7A1 (1). Type VII collagen is the main component of anchoring fibrils, structures that support anchorage of the epidermis to the underlying dermis (2).…”

Section: Introductionmentioning

confidence: 99%

Fibroblast-Derived Dermal Matrix Drives Development of Aggressive Cutaneous Squamous Cell Carcinoma in Patients with Recessive Dystrophic Epidermolysis Bullosa

et al. 2012

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Patients with the genetic skin blistering disease recessive dystrophic epidermolysis bullosa (RDEB) develop aggressive cutaneous squamous cell carcinoma (cSCC). Metastasis leading to mortality is greater in RDEB than in other patient groups with cSCC. Here we investigate the dermal component in RDEB using mRNA expression profiling to compare cultured fibroblasts isolated from individuals without cSCC and directly from tumor matrix in RDEB and non-RDEB samples. Although gene expression of RDEB normal skin fibroblasts resembled that of cancer-associated fibroblasts, RDEB cancer-associated fibroblasts exhibited a distinct and divergent gene expression profile, with a large proportion of the differentially expressed genes involved in matrix and cell adhesion. RDEB cancer-associated fibroblasts conferred increased adhesion and invasion to tumor and nontumor keratinocytes. Reduction of COL7A1, the defective gene in RDEB, in normal dermal fibroblasts led to increased type XII collagen, thrombospondin-1, and Wnt-5A, while reexpression of wild type COL7A1 in RDEB fibroblasts decreased type XII collagen, thrombospondin-1, and Wnt-5A expression, reduced tumor cell invasion in organotypic culture, and restricted tumor growth in vivo. Overall, our findings show that matrix composition in patients with RDEB is a permissive environment for tumor development, and type VII collagen directly regulates the composition of matrix proteins secreted by dermal and cancer-associated fibroblasts.

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Section: Introductionmentioning

confidence: 99%

Fibroblast-Derived Dermal Matrix Drives Development of Aggressive Cutaneous Squamous Cell Carcinoma in Patients with Recessive Dystrophic Epidermolysis Bullosa

et al. 2012

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“…Epitopes recognized by the majority of EBA sera were mapped to the noncollagenous 1 (NC1) domain of type VII collagen (5)(6)(7)(8)(9). The essential role that type VII collagen plays in the biology of the DEJ is exemplified by inherited or targeted disruptions in the gene that encodes it, which yield a phenotype characterized by subepidermal blisters (10)(11)(12)(13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Induction of dermal-epidermal separation in mice by passive transfer of antibodies specific to type VII collagen

Sitaru¹,

Mihai²,

Otto³

et al. 2005

J. Clin. Invest.

223

272

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Epidermolysis bullosa acquisita (EBA) is a subepidermal blistering disorder associated with tissue-bound and circulating autoantibodies specific to type VII collagen, a major constituent of the dermal-epidermal junction. Previous attempts to transfer the disease by injection of patient autoantibodies into mice have been unsuccessful. To study the pathogenic relevance of antibodies specific to type VII collagen in vivo, we generated and characterized rabbit antibodies specific to a murine form of this antigen and passively transferred them into adult nude, BALB/c, and C57BL/6 mice. Immune rabbit IgG bound to the lamina densa of murine skin and immunoblotted type VII collagen. Mice injected with purified IgG specific to type VII collagen, in contrast to control mice, developed subepidermal skin blisters, reproducing the human disease at the clinical, histological, electron microscopical, and immunopathological levels. Titers of rabbit IgG in the serum of mice correlated with the extent of the disease. F(ab′) 2 fragments of rabbit IgG specific to type VII collagen were not pathogenic. When injected into C5-deficient mice, antibodies specific to type VII collagen failed to induce the disease, whereas C5-sufficient mice were susceptible to blister induction. This animal model for EBA should facilitate further dissection of the pathogenesis of this disease and development of new therapeutic strategies.

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“…The pathogenic role of AFs in stabilizing the BMZ has been confirmed by EM observations of them being abnormal, diminished or absent, and by the immunohistochemical finding that type VII collagen is reduced or absent in the group of inherited skin diseases collectively known as dystrophic EB (19)(20)(21)(22). All forms of dystrophic EB were recently found to be directly caused by mutations in the type VII collagen gene (COL7A1) (23)(24)(25)(26). Conversely, acquired production of autoantibodies to AFs directed against the NC-1 domain of type VII collagen, leads to EB acquisita, an autoimmune blistering disease (27).…”

Section: I) Anchoring Fibrils (Afs) Originate and Terminate In The Lamentioning

confidence: 71%

New insights into the immunoultrastructural organization of cutaneous basement membrane zone molecules

Shimizu

1998

Experimental Dermatology

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The epidermal basement membrane zone (BMZ) is composed of various molecules, each of which plays an important role in dermoepidermal adhesion. Genetic abnormality of certain BMZ molecules leads to an inherited group of skin diseases collectively referred to as epidermolysis bullosa, whose hallmark is skin fragility of varying degrees. Furthermore, development of autoantibodies to certain BMZ molecules leads to the onset of a number of acquired autoimmune blistering diseases in which dermo-epidermal separation occurs, including bullous pemphigoid and epidermolysis bullosa acquisita. The ultrastructural location of each BMZ molecule has been studied using a range of immunoelectron microscopy (immuno-EM) techniques. Recent technical advances in imKey words: immunoelectron microscopymuno-EM and in molecular engineering for production of epitope-speci- to these findings, this review focuses on three major BMZ-related mol-

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A missense mutation in type VII collagen in two affected siblings with recessive dystrophic epidermolysis bullosa

Cited by 184 publications

References 32 publications

Fibroblast-Derived Dermal Matrix Drives Development of Aggressive Cutaneous Squamous Cell Carcinoma in Patients with Recessive Dystrophic Epidermolysis Bullosa

Fibroblast-Derived Dermal Matrix Drives Development of Aggressive Cutaneous Squamous Cell Carcinoma in Patients with Recessive Dystrophic Epidermolysis Bullosa

Induction of dermal-epidermal separation in mice by passive transfer of antibodies specific to type VII collagen

New insights into the immunoultrastructural organization of cutaneous basement membrane zone molecules

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