Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Generalized atrophic benign epidermolysis bullosa (GABEB) is a nonlethal form of junctional epidermolysis bullosa characterized by generalized skin and mucosal blisters that heal with atrophy; other features include alopecia, nail dystrophy, large melanocytic nevi, and autosomal recessive inheritance. The specific aim of this study was to identify an abnormality in epidermal basement membrane adhesion molecules in well characterized GABEB patients that would explain why these subjects' epidermis separates from their epidermal basement membrane. Cryostat sections of nonlesional skin from 8 GABEB patients in 5 different families as well as skin from normal volunteers (controls) were studied by indirect immunofluorescence microscopy using rabbit antiserum directed against a BPAG1 fusion protein or monoclonal antibodies directed against the extracellular domain of BPAG2 (HD18 and 233), epiligrin (P1E1), laminin 5 (GB3), types IV and VII collagen, or integrin subunits alpha 2, alpha 3, beta 1, alpha 6, or beta 4. In these studies, monoclonal antibodies HD18 and 233 showed no reactivity and diminished reactivity, respectively, to the epidermal BM of all GABEB patients. Interestingly, in one patient, the absent or diminished reactivities of monoclonal anti-BPAG2 antibodies were limited to well demarcated portions of an otherwise intact epidermal basement membrane. Moreover, BPAG1, epiligrin, laminin 5, types IV and VII collagen, and all integrin subunits under study were expressed in the same manner in both GABEB and normal human skin. These findings identify an abnormality in the extracellular domain of BPAG2 in the skin of GABEB patients. BPAG2 (type XVII collagen) is a transmembrane, hemidesmosome-associated molecule whose extracellular domain resides at the exact level where blisters develop in the skin of patients with GABEB.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diminished expression of the extracellular domain of bullous pemphigoid antigen 2 (BPAG2) in the epidermal basement membrane of patients with generalized atrophic benign epidermolysis bullosa. 853 14

Junctional EB was once considered a uniformly fetal autosomal recessive skin disease. One of the first and best characterized forms of generalized JEB that has a more favorable prognosis was GABEB. Since its initial description in 1976, many additional cases have been compiled, all sharing the features of chronic blistering from birth, nail dystrophy, hair loss, and abnormal teeth. In addition, some patients have large melanocytic nevi that form at sites of prior blisters. The first clues as to the protein defective in these patients was provided by immunofluorescence microscopy studies, which showed absent or decreased expression of type XVII collagen in these patient's epidermal BM. This protein was a promising candidate because it is located in the ultrastructural plane where blisters from in patients with GABEB. It is also the same hemidesmosomal protein against which antibodies are directed in patients with autoimmune blistering diseases: bullous, gestational, and cicatricial pemphigoid. The demonstration of decreased expression of type XVII collagen in patients with GABEB pointed the way to a crucial distinction that could not be based on clinical and histologic findings--that of discriminating infants with GABEB from those with the lethal Herlitz variant of JEB. These two diseases may be differentiated because decreased expression of type XVII collagen is found exclusively in GABEB, whereas decreased expression of laminin 5 is most likely associated with Herlitz JEB. The molecular basis of GABEB has been determined. The immunofluorescence microscopy studies mentioned above directed mutation studies to the COL17A1 gene. Several mutations in COL17A1 have been described in patients with GABEB, almost all of which result in a PTC. As a consequence of the PTC, mutant COL17A1 transcripts are rapidly degraded by nonsense-mediated mRNA decay, blocking production of type XVII collagen from the mutant allele. Heterozygous carriers of the mutation are thus rendered untouched by the mutation. In the homozygous state, however, this results in the absence of this vital adhesion protein, leading to chronic blistering and skin fragility observed in these patients. These studies also significantly increase our knowledge about the normal functions of type XVII collagen. The fact that patients deficient in type XVII collagen have fragile skin attests to the role of this protein in the adhesion of basal keratinocytes to epidermal BM. The severity of GABEB, however, is much less than that observed in patients with a complete deficiency of laminin 5, suggesting that type XVII collagen functions cooperatively with other hemidesmosomal proteins in promoting adhesion. Studies using GABEB keratinocytes will help characterize these kinds of interactions. The ultimate prospect of mutation analysis in these patients is the hope of correcting their genetic defect and curing their disease. Until then, the physician plays an important role in making the diagnosis, providing general supportive skin care, advising avoidance of trauma, treating infections, and supporting the patient's psychosocial development. Further studies of patients with GABEB will lead to new therapeutic approaches, as well as reveal additional complex functions of type XVII collagen not only in skin, but also in hair, teeth, and nails.
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PMID:Generalized atrophic benign epidermolysis bullosa. 955 Nov 42

Generalized atrophic benign epidermolysis bullosa (GABEB) is a nonlethal form of junctional epidermolysis bullosa. The expression of type XVII collagen (180 kDa bullous pemphigoid antigen) or of laminin 5 is markedly reduced in the skin. A 13-year-old patient with GABEB, developed several large, asymmetric, irregularly pigmented melanocytic nevi with poorly defined borders. They had appeared following blister formation since 8 years of age. Histological examination revealed an irregular proliferation of monomorphous melanocytes at the dermoepidermal junction. Small nests of melanocytes were focally present. This case further emphasizes the difficulty in differentiating nevi appearing in GABEB from malignant melanoma.
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PMID:[Large melanocytic nevi in generalized atrophic benign epidermolysis bullosa (epidermolysis bullosa nevi)]. 1157 74