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)

Distal myopathies are a heterogeneous group of genetic disorders characterized clinically by progressive muscular weakness and atrophy beginning in the hands or feet, and pathologically by myopathic changes in skeletal muscles. Five distinct distal myopathies are identified, among them four have been recently defined by their gene and causative mutations. They are classified according to age at onset, mode of inheritance, and muscle groups initially involved into the following: Laing myopathy (infancy onset, autosomal dominant inheritance, onset in anterior compartment of legs) caused by mutations in a myosin gene (MYH7) on chromosome 14q; Nonaka myopathy (early adult onset, autosomal recessive inheritance, onset in anterior compartment of legs), identical to quadriceps-sparing familial inclusion myopathy, caused by mutations in the GNE gene on chromosome 9p-q; Miyoshi myopathy (early adult onset, autosomal recessive inheritance, onset in posterior compartment of legs) caused by mutations in the dysferlin gene on chromosome 2p; Welander myopathy (late adult onset, autosomal dominant inheritance, onset in hands) linked to chromosome 2p; Udd/Markesbery-Griggs myopathy (late adult onset, autosomal dominant inheritance, onset in anterior compartment of legs) caused by mutations in the titin gene on chromosome 2q. Except for Miyoshi myopathy, which has a striking elevated serum creatine kinase level and the typical findings of muscular dystrophy, most of the distal myopathies have normal or midly elevated creatine kinase levels and share the common pathologic feature of rimmed vacuoles.
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PMID:[Distal myopathies]. 1503 79

An increasing number of genes encoding for putative or demonstrated glycosyltransferases are being associated with muscular dystrophies of variable severity, ranging from severe congenital onset and associated structural eye and brain changes, to relatively mild forms with onset into adulthood. Five of these genes (POMT1; POMGnT1; FXRP; Fukutin; LARGE) encode for proteins involved in the glycosylation of alpha-dystroglycan and, indeed, abnormal glycosylation of this molecule is a common finding in all the respective conditions (Walker Warburg syndrome; Muscle-Eye-Brain disease; congenital muscular dystrophy type 1C and Limb girdle muscular dystrophy type 21; Fukuyama muscular dystrophy; congenital muscular dystrophy type 1D). A 6th gene, GNE, responsible for the hereditary form of inclusion body myositis, encodes for a glycosyltransferase the substrate(s) of which is, however, still unclear. This article provides an overview of the clinical, biochemical and genetic features of this group of disorders.
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PMID:Journey into muscular dystrophies caused by abnormal glycosylation. 1560 48

Oculopharyngodistal myopathy is a rare type of hereditary myopathy characterised pathologically by the changes of muscular dystrophy with rimmed vacuoles and intra-muscular tubulofilamentous inclusions. Here we report the clinical and myopathological changes in a Chinese family with oculopharyngodistal myopathy. The proband showed external ophthalmoplegia, dysphagia, distal weakness and atrophy in all extremities. Serum creatine kinase level was mildly elevated and a myopathic pattern with myotonic discharge was demonstrated by electromyography (EMG). Molecular genetic analysis showed that the number of trinucleotide repeat expansions in the polyadenylate-binding protein nuclear 1 gene was within the normal limit. No mutations were indentified in the GNE gene. Five other persons with similar symptoms were found in the same generation. Muscle biopsy was performed on the tibialis anterior muscle in the proband. Muscular dystrophy changes with rimmed vacuoles were the main histopathological changes. Ultrastructural examination revealed numerous tubulofilamentous inclusions in both sarcoplasm and nucleus. EMG showed myotonic discharges in oculopharyngodistal myopathy. In addition to the sarcoplasm inclusions, we confirmed that tubulofilamentous inclusions appeared also in the nucleus.
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PMID:The clinical and myopathological features of oculopharyngodistal myopathy in a Chinese family. 1850 9

Remudy (Registry of Muscular Dystrophy), operated by NCNP (the National Center of Neurology and Psychiatry), Japan, runs two national registries for Dystrophinopathy and GNE myopathy in collaboration with the TREAT-NMD (Translational Research in Europe--Assessment and Treatment of Neuromuscular Disease) alliance. The aim of Remudy is to construct a clinical research infrastructure that accelerates the pace of clinical development research for these rare diseases. We successfully provide data sets for feasibility studies, send out appropriate information about clinical trials to speed up the recruitment of candidates, as well as present the natural history and epidemiology data of these rare diseases using a new 'registry based' research style. Remudy presents a prototype model of the clinical research infrastructure to overcome these rare and incurable diseases.
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PMID:[Remudy]. 2540 75

Remudy, operated by the NCNP, runs two national registries for Dystrophinopathy and GNE myopathy in Japan under the collaboration with the TREAT-NMD alliance. The aim is to construct the clinical research infrastructure and accelerate the clinical development research for these rare diseases. We successfully provide the data sets for the feasibility studies, send out the appropriate information of the clinical trials for the candidates to speed up the recruitment for trials, collaboration with the Muscular Dystrophy Clinical Trial Network: MDCTN, as well as present the natural history and epidemiological data of the rare diseases with a new 'registry based' research style. Remudy provides a prototype of the clinical research infrastructure to over come the rare and incurable diseases.
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PMID:[Infrastructure for the clinical research of muscular dystrophies: remudy and MDCTN]. 2551 64

UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) is the key enzyme for the biosynthesis of sialic acids. Sialic acids are terminal monosaccharides of glycoconjugates and gangliosides, which have an essential influence on various cell interactions. The sialylation of proteins varies during development, aging, and pathogenesis of degenerative diseases such as Morbus Alzheimer, diabetes mellitus type II, or myopathies. Mutation of methionine 743 in the GNE leads to a 30% reduction of the enzyme activity and is responsible for an aggressive form of GNE myopathy. GNE myopathy or hereditary inclusion body myopathy (HIBM) is an age-dependent muscular dystrophy. Here, we analyzed the impact of the exchange of methionine to threonine at position 743 which introduces an additional potential phosphorylation/O-GlcNAcylation site. We found increased O-GlcNAcylation of the M743T variant compared to the wild-type GNE. In addition, removal of the O-GlcNAc of the M743T variant resulted in an increased activity comparable to activity of the wild-type GNE. Furthermore, the half-life of the M743T variant is two times longer than for the wild-type GNE protein. This study provides that the balance of phosphorylation and O-GlcNAcylation is decisive involved in efficiency and regulation of GNE.
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PMID:Aberrant O-GlcNAcylation disrupts GNE enzyme activity in GNE myopathy. 2703 41