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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intermediate filament (IF) proteins and the dystrophin-associated protein complex (DPC) play important roles in cardiac and skeletal muscle. Both systems are mutated in several different forms of inherited muscular dystrophy and cardiomyopathy. Recently two articles have been published that propose a physical link between the DPC and the IF network in muscle. Two novel IF proteins, syncoilin and desmuslin, have been identified as binding partners for the dystrophin-associated protein, alpha-dystrobrevin, in muscle. These novel interactions suggest that alpha-dystrobrevin may tether the IF protein network to the DPC. Mice lacking alpha-dystrobrevin develop muscular dystrophy without perturbing the assembly of the DPC at the muscle membrane, suggesting the involvement of other non-DPC proteins in the disease. The interaction between the DPC and the IF network may be disrupted in patients with Duchenne muscular dystrophy and in mice lacking alpha-dystrobrevin.
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PMID:Intermediate filaments and the function of the dystrophin-protein complex. 1216 Oct 77

Mutations of the human plectin gene (PLEC) on chromosome 8q24 cause autosomal recessive epidermolysis bullosa simplex with muscular dystrophy (EBS-MD). In the present study we analyzed the downstream effects of PLEC mutations on plectin protein expression and localization, the structure of the extrasarcomeric desmin cytoskeleton, protein aggregate formation and mitochondrial distribution in skeletal muscle tissue from three EBS-MD patients. PLEC gene analysis in a not previously reported 35-year-old EBS-MD patient with additional disease features of cardiomyopathy and malignant arrhythmias revealed novel compound heterozygous (p.(Phe755del) and p.(Lys1040Argfs*139)) mutations resulting in complete abolition of plectin protein expression. In contrast, the other two patients with different homozygous PLEC mutations showed preserved plectin protein expression with one only expressing rodless plectin variants, and the other markedly reduced protein levels. Analysis of skeletal muscle tissue from all three patients revealed severe disruption of the extrasarcomeric intermediate filament cytoskeleton, protein aggregates positive for desmin, syncoilin, and synemin, degenerative myofibrillar changes, and mitochondrial abnormalities comprising respiratory chain dysfunction and an altered organelle distribution and amount.Our study demonstrates that EBS-MD causing PLEC mutations universally result in a desmin protein aggregate myopathy phenotype despite marked differences in individual plectin protein expression patterns. Since plectin is the key cytolinker protein that regulates the structural and functional organization of desmin filaments, the defective anchorage and spacing of assembled desmin filaments is the key pathogenetic event that triggers the formation of desmin protein aggregates as well as secondary mitochondrial pathology.
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PMID:Downstream effects of plectin mutations in epidermolysis bullosa simplex with muscular dystrophy. 2712 71