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)

With few exceptions, epidermolysis bullosa (EB) simplex is an autosomal dominant disorder characterized by rather localized and recurrent nonscarring blister formation; mucous membranes and other organs are usually uninvolved. Recently, two patients were described with an autosomal recessive form of EB simplex associated with muscular dystrophy. We now describe four additional patients with autosomal recessive EB simplex, three of whom had associated muscular dystrophy or congenital myasthenia gravis. These patients had generalized cutaneous findings, including milia, atrophic scarring, nail dystrophy, and scalp alopecia, which have been classically attributed to either junctional or dystrophic EB. Each patient had significant oral cavity involvement, and in two, marked growth retardation and anemia were also present. Our findings suggest that autosomal recessive EB simplex may be characterized by rather severe cutaneous and extracutaneous disease activity, and may be associated with at least two distinct neuromuscular diseases.
Arch Dermatol 1989 Jul
PMID:Autosomal recessive epidermolysis bullosa simplex. Generalized phenotypic features suggestive of junctional or dystrophic epidermolysis bullosa, and association with neuromuscular diseases. 266 9

Epidermolysis bullosa with unusually severe clinical features was associated with progressive muscular dystrophy in two siblings. Light and electron microscopic examination revealed an intraepidermal cleavage confirming that this mechanobullous disease belonged to the epidermolysis bullosa simplex group. This may represent a new disease entity inherited in an autosomal-recessive fashion.
Arch Dermatol 1988 Apr
PMID:Epidermolysis bullosa simplex associated with muscular dystrophy with recessive inheritance. 335 99

We report an infant with a rare form of epidermolysis bullosa simplex characterized by an autosomal recessive pattern of inheritance, severe cutaneous involvement, oral and nail lesions, associated with muscular dystrophy, and a poor prognosis, due to extracutaneous disease. In addition to the usual presentation of this disease, our patient had severe anemia, with immature circulating white cells, and bone marrow histology suggestive of a pre-leukemic state, a finding which has not before been reported in the literature.
Pediatr Dermatol 1994 Dec
PMID:Epidermolysis bullosa simplex associated with muscular dystrophy: a new case. 789 87

Recent progress in understanding the molecular organization of the cutaneous basement membrane zone (BMZ) has revealed an intricate network of structural proteins necessary for stable association of the epidermis to the underlying dermis. Molecular genetics of the cutaneous BMZ has also revealed that defects in as many as nine distinct genes within the dermal-epidermal junction which result in different forms of epidermolysis bullosa (EB), a group of heritable mechano-bullous disorders. We have recently demonstrated that a variant of EB associated with late-onset development of muscular dystrophy (EB-MD, MIM no. 226670) results from mutations in the gene encoding plectin (PLEC1), a cytoskeleton associated attachment protein present in the hemidesmosomal inner plaque and the sarcolemma of the muscle. Consequently, mutations in this multi-functional gene/protein system can result in phenotypic manifestations of EB-MD both in the skin and the muscle. In this overview, we will summarize the domain organization of plectin and the structure of the corresponding gene (PLEC1), as well as the genetic basis of EB-MD in families studied thus far. Elucidation of the molecular basis of this subtype of EB adds to our understanding of the structural and functional complexity of the cutaneous BMZ.
Exp Dermatol 1996 Oct
PMID:Plectin and human genetic disorders of the skin and muscle. The paradigm of epidermolysis bullosa with muscular dystrophy. 898 Oct 21

Keratins are heteropolymeric proteins which form the intermediate filament cytoskeleton in epithelial cells. Since 1991, mutations in several keratin genes have been found to cause a variety of human diseases affecting the epidermis and other epithelial structures. Epidermolysis bullosa simplex (EBS) was the first mechanobullous disease for which the underlying genetic lesion was found, with mutations in both the K5 and K14 genes rendering basal epidermal keratinocytes less resilient to trauma, resulting in skin fragility. The site of mutation in the keratin protein correlates with phenotypic severity in this disorder. Since mutations were identified in the basal cell keratins, the total number of keratin genes associated with diseases has risen to eleven. The rod domains of suprabasal keratins K1 and K10 are mutated in bullous congenital ichthyosiform erythroderma (BCIE; also called epidermolytic hyperkeratosis, EH) and mosaicism for K1/K10 mutations results in a nevoid distribution of EH. An unusual mutation in the VI domain of K1 has also been found to cause diffuse non-epidermolytic palmoplantar keratoderma (DNEPPK). Mutations in palmoplantar specific keratin K9 cause epidermolytic palmoplantar keratoderma (EPPK) and mutations in the late differentiation suprabasal keratin K2e cause ichthyosis bullosa of Siemens (IBS). In the last year or so, mutations were discovered in differentiation specific keratins K6a and K16 causing pachyonychia congenita type 1 and K17 mutations occur in pachyonychia congenita type 2. K16 and K17 mutations have also been reported to produce phenotypes with little or no nail changes: K16 mutations can present as focal non-epidermolytic palmoplantar keratoderma (NEPPK) and K17 mutations can result in a phenotype resembling steatocystoma multiplex. Recently, mutation of mucosal keratin pair K4 and K13 has been shown to underlie white sponge nevus (WSN). This year, the first mutations in a keratin-associated protein, plectin, were shown to cause a variant of epidermolysis bullosa associated with late-onset muscular dystrophy (MD-EBS). An unusual mutation has been identified in K5 which is responsible for EBS with mottled pigmentation and genetic linkage analysis suggests that the hair disorder monilethrix is likely to be due to a mutation in a hair keratin. The study of keratin diseases has led to a better understanding of the importance of the intermediate filament cytoskeleton and associated connector molecules in maintaining the structural integrity of the epidermis and other high stress epithelial tissues, as well as allowing diagnosis at the molecular level thus facilitating prenatal testing for this heterogeneous group of genodermatoses.
Exp Dermatol 1996 Dec
PMID:Human keratin diseases: hereditary fragility of specific epithelial tissues. 902 91

Plectin is a 500 kDa protein involved in cytoskeleton-plasma membrane attachment with a wide tissue distribution including cutaneous and airway epithelia, muscle and neuronal tissue. Recently, mutations in the gene encoding plectin (PLEC1) have been implicated in the pathogenesis of an autosomal recessive variant of epidermolysis bullosa simplex in which cutaneous blistering starting in the neonatal period is associated with muscular dystrophy in later life. In this study, we report two unrelated patients, both of consanguineous parentage, who presented with cutaneous blistering and a hoarse cry from birth. Both experienced inspiratory stridor and respiratory distress, necessitating emergency tracheostomy in one case. Immunoreactivity to monoclonal antibodies against plectin was absent or markedly reduced in skin biopsies from both patients. Electron microscopy revealed a low intraepidermal plane of cleavage and hypoplastic hemidesmosomes with a reduced association with keratin intermediate filaments. Direct sequencing of PLEC1 in each case demonstrated two novel homozygous frameshift deletion mutations, 5069del19 and 5905del2, which both create downstream premature termination codons. Although currently neither patient has symptoms of muscle disease, the identification of mutations in PLEC1 may be predictive for the future development of muscular dystrophy. Recessive epidermolysis bullosa simplex resulting from abnormalities in plectin should be considered in the differential diagnosis blistering, hoarseness and stridor in infancy.
Br J Dermatol 1997 Dec
PMID:Recessive epidermolysis bullosa simplex associated with plectin mutations: infantile respiratory complications in two unrelated cases. 947 Sep 5

Epidermolysis bullosa (EB), a heterogeneous group of genodermatoses, is characterized by fragility and blistering of the skin, associated with characteristic extracutaneous manifestations. Based on clinical severity, constellation of the phenotypic manifestations, and the level of tissue separation within the cutaneous basement membrane zone, EB has been divided into distinct subcategories. Traditionally, these include the simplex, junctional and dystrophic variants of EB. Recent attention has been drawn to variants of EB demonstrating tissue separation at the level of hemidesmosomes, ultrastructurally recognizable adhesion complexes within the cutaneous basement membrane zone. Clinically, these hemidesmosomal variants manifest either as generalized atrophic benign epidermolysis bullosa (GABEB), EB with pyloric atresia, or EB with late-onset muscular dystrophy. Elucidation of basement membrane zone components by molecular cloning and development of mutation detection strategies have revealed that the hemidesmosomal variants of EB result from mutations in the genes encoding the subunit polypeptides of the 180-kD bullous pemphigoid antigen/type XVII collagen, the alpha6beta4 integrin, or plectin, respectively. Collectively, these data add to the understanding of the molecular complexity of the cutaneous basement membrane zone in EB, as attested by the fact that mutations in 10 different genes can underlie different variants of EB. Elucidation of mutations in different forms of EB has direct application to genetic counseling and DNA-based prenatal testing in families with EB.
Exp Dermatol
PMID:Hemidesmosomal variants of epidermolysis bullosa. Mutations in the alpha6beta4 integrin and the 180-kD bullous pemphigoid antigen/type XVII collagen genes. 958 44

Epidermolysis bullosa with muscular dystrophy (EB-MD) is a distinct variant of EB caused by mutations in the plectin gene (PLEC1). In this study, we have examined two Japanese patients with EB-MD using heteroduplex scanning or a protein truncation test for mutation detection analysis. The results revealed that both patients were compound heterozygotes for novel PLEC1 mutations (Q1936X/Q1053X and R2421X/12633ins4), which all caused premature termination of translation of the corresponding polypeptides. These cases, which demonstrate the utility of two complementary mutation detection strategies, add to the repertoire of plectin mutations in EB-MD.
J Invest Dermatol 1999 Jan
PMID:Four novel plectin gene mutations in Japanese patients with epidermolysis bullosa with muscular dystrophy disclosed by heteroduplex scanning and protein truncation tests. 988 73

Plectin, a widespread cytoskeletal linker protein, is prominently expressed in basal keratinocytes of the epidermis. HD1, originally identified as a hemidesmosomal protein, has been suggested to be an isoform of or closely related to plectin, but the exact relationship between these proteins is unknown. Plectin has recently been identified as the gene/protein system at fault in epidermolysis bullosa simplex associated with muscular dystrophy (EBS-MD; OMIM# 226670). In this study, we examined the expression patterns of plectin and HD1 epitopes in the skin of four unrelated patients with EBS-MD confirmed to be caused by plectin gene mutations. By indirect immunofluorescence, all monoclonal antibodies (mAbs) to plectin (5B3, 10F6) or to HD1 (121, E2, K15, 156) bound to the epidermal basement membrane zone (BMZ) of normal human skin. In addition, immunostaining along the periphery of keratinocytes was detected with mAbs 5B3, 10F6 (antiplectin), K15 and 156 (anti-HD1), but not with mAbs 121 and E2 (anti-HD1). Immunolabeling for mAbs 5B3 and 10F6 (antiplectin) was absent in the skin of three patients who had premature termination codon mutations in the plectin gene in both alleles. In contrast, labeling was only slightly reduced in a patient who was homozygous for a 9-bp in-frame deletion mutation in the same gene. Interestingly, peripheral labeling of keratinocytes using mAbs K15 and 156 (anti-HD1) was clearly present in all the patients despite the disappearance of BMZ labeling. Quantitative analysis by postembedding immunoelectron microscopy demonstrated that both plectin and HD1 epitopes were localized in the inner plaque of hemidesmosomes with a mean distance of 110 and 120 nm from the plasma membrane, respectively. These results confirm the molecular heterogeneity of EBS-MD in terms of the expression patterns of plectin and HD1 epitopes which correlate with clinical severity, the pattern of plectin gene mutations and their consequences.
Arch Dermatol Res 1999 Oct
PMID:Expression of plectin and HD1 epitopes in patients with epidermolysis bullosa simplex associated with muscular dystrophy. 1055 10

We report a novel case of epidermolysis bullosa simplex with severe mucous membrane involvement and mutations in the plectin gene (PLEC1). The patient suffered from extensive blistering of the skin and oral and laryngeal mucous membranes. Electron microscopy of a lesional skin biopsy showed cleft formation within the basal cell layer of the epidermis. Antigen mapping displayed entirely negative staining for plectin, a large (>500 kDa) multifunctional adhesion protein present in hemidesmosomes of the basal keratinocytes. Mutation analysis revealed compound heterozygous, previously undisclosed nonsense mutations, Q1713X and R2351X, of paternal and maternal origin, respectively, within exon 32 of PLEC1. Based on earlier reports, plectin deficiency is associated with late onset muscular dystrophy in patients with epidermolysis bullosa. No signs of muscle weakness have been observed during the 4 y follow-up of our patient. This case illustrates the fact that molecular pathological analyses have prognostic implications in identification and evaluation of patients who appear to be at risk for development of muscular dystrophy later in life.
J Invest Dermatol 2000 Feb
PMID:Mutation reports: epidermolysis bullosa simplex associated with severe mucous membrane involvement and novel mutations in the plectin gene. 1065 1


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