Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The laminins are a family of structural basement membrane components with major influences on cells. They are high molecular weight glycoproteins composed of three different but homologous chains, alpha, beta and gamma. At present 10 different chains have been identified. Each chain has a distinct structural organization of domains, some of which have been assigned biological activities, including self-assembly and interactions with other proteins. The particular importance of laminins for the formation and stability of cell adhesion complexes is highlighted in severe inherited diseases of muscle and skin. Merosin is the collective name for laminins that share a common subunit, the laminin alpha 2 chain. Merosin-deficient congenital muscular dystrophy (CMD) is caused by mutations in the laminin alpha 2 chain gene. The skin disease Herlitz junctional epidermolysis bullosa is caused by mutations in any of the laminin alpha 3, beta 3 or gamma 2 chain genes. The medical importance of laminins provides a further impetus to study the basic structure-function relationships in laminins in order to understand genotype-phenotype relationships and to design prenatal diagnostic tests and therapies aimed at compensating for specific defects.
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PMID:Merosin/laminin-2 and muscular dystrophy. 902 48

Cutaneous basement membrane zone (BMZ) consists of a number of attachment structures that are critical for stable association of the epidermis to the underlying dermis. These include hemidesmosomes, anchoring filaments and anchoring fibrils which form an interconnecting network extending from the intracellular milieu of basal keratinocytes across the dermal-epidermal basement membrane to the underlying dermis. Aberrations in this network structure, e.g. due to genetic lesions in the corresponding genes, can result in fragility of the skin at the level of the cutaneous BMZ. The prototype of such diseases is epidermolysis bullosa (EB), a heterogeneous group of genodermatoses characterized by fragility and blistering of the skin, often associated with extracutaneous manifestations, and inherited either in an autosomal dominant or autosomal recessive manner. Based on constellations of the phenotypic manifestations, severity of the disease, and the level of tissue separation within the cutaneous BMZ, EB has been divided into clinically distinct subcategories, including the simplex, hemidesmosomal, junctional and dystrophic variants. Elucidation of BMZ gene/protein systems and development of mutation detection strategies have allowed identification of mutations in 10 different BMZ genes which can explain the clinical heterogeneity of EB. These include mutations in the type VII collagen gene (COL7A1) in the dystrophic (severely scarring) forms of EB; mutations in the laminin 5 genes (LAMA3, LAMB3 and LAMC2) in a lethal (Herlitz) variant of junctional EB; aberrations in the type XVII collagen gene (COL17A1) in non-lethal forms of junctional EB; mutations in the alpha6 and beta4 integrin genes in a distinct hemidesmosomal variant of EB with congenital pyloric atresia; and mutations in the plectin gene (PLEC1) in a form of EB associated with late-onset muscular dystrophy. Identification of mutations in these gene/protein systems attests to their critical importance in the overall stability of the cutaneous BMZ. Furthermore, elucidation of mutations in different variants of EB has direct clinical applications in terms of refined classification, improved genetic counseling, and development of DNA-based prenatal testing in families with EB.
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PMID:Mutation analysis and molecular genetics of epidermolysis bullosa. 1036 29

Anchoring complexes are specialized focal attachment sites within the cutaneous basement membrane zone (BMZ) and play a crucial role in dermo-epidermal adhesion. Structural weakness that may be caused by the binding of autoantibodies to components of the anchoring complex or by aberrant expression of these components as a result of genetic defects can lead to subepidermal blisters. Autoimmune subepidermal blistering disorders include bullous pemphigoid, pemphigoid gestationis, lichen planus pemphigoides, linear IgA disease, cicatricial pemphigoid, anti-p200, anti-p105, and anti-p450 pemphigoid, epidermolysis bullosa acquisita, and bullous systemic lupus erythematosus. The autoantigen in the skin of patients with dermatitis herpetiformis remains to be identified. More than 300 distinct mutations in 10 different genes corresponding to structural components of the BMZ have been described that result in skin fragility and dermo-epidermal separation associated with characteristic extracutaneous manifestations. This group of genodermatoses, collectively referred to as epidermolysis bullosa (EB), consists of distinct variants, such as EB simplex, EB with muscular dystrophy, EB with pyloric atresia, generalized atrophic benign EB, Herlitz junctional EB, and dystrophic EB. Recent advances in the molecular characterization of BMZ components have led to a better understanding of the interaction between these molecules as well as the autoimmune response against these proteins. In addition, by the elucidation of genetic defects in the different variants of EB, genotype-phenotype correlations now begin to arise and genetic counseling has been improved.
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PMID:Autoimmune and inherited subepidermal blistering diseases: advances in the clinic and the laboratory. 1109 26