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)

Much progress has been made over the last few years in understanding and classifying neuromuscular diseases. The heart is frequently affected but often in a dissociated manner with respect to the neuromuscular signs although it has a significant impact on the prognosis. In children and adolescents, the dystrophinopathies, especially Duchenne's muscular dystrophy, are the principal problems but the mild arrhythmic events observed seem to be related to left ventricular dysfunction. On the other hand, in myotonic dystrophies (Steinert's disease), ventricular arrhythmias or conduction defects may appear at an early stage of the disease with serious consequences justifying appropriate follow-up and invasive preventive measures. Emery Dreifuss X-linked dystrophy and other laminopathies are rare conditions but are associated with sudden death and cardiomyopathies of the young adult. Specialised cardiological follow-up is justified in childhood from the time of diagnosis. Medication or implantable electric devices may be justified before the end of the second decade of life. Progressive infra-hisian conduction defects have also been reported in Kearns-Sayre oculo-pharyngeal myopathy. Prospective studies are required at this age to determine the natural history of these pathologies that are probably under diagnosed. The present recommendations, which are based mainly on data from adult series, could then be adapted for younger patients.
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PMID:[Arrhythmia follow-up of children and adolescents with neuromuscular diseases]. 1764 81

The case of a family in which several members displayed conduction defects inherited as a dominant trait is reported. The proband was a young woman with a 1st degree atrio-ventricular block and high serum creatine kinase. Several members of the family featured cardiologic symptoms. All adult family members were clinically evaluated and blood tests including serum creatine-kinase levels, standard and Holter ECG, echocardiogram and muscle MRI were performed. LMNA gene analysis was carried out and a novel missense mutation consisting in substitution of exon 4 c.799 T/C, p.Tyr267His was revealed. The mutation was present in seven family members, five of whom displayed cardiac defects alone with no involvement of the skeletal muscle. In all mutated individuals muscle MRI featured a pattern of skeletal muscle involvement similar to that observed in autosomal dominant Emery Dreifuss muscular dystrophy, suggesting that even patients bearing a LMNA gene mutation associated to an apparently selective cardiac phenotype may present subclinical skeletal muscle involvement.
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PMID:Muscle MRI findings in patients with an apparently exclusive cardiac phenotype due to a novel LMNA gene mutation. 1833 98

Mutations in the LMNA gene result in diverse phenotypes including Emery Dreifuss muscular dystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy with conduction system disease, Dunnigan type familial partial lipodystrophy, mandibulo acral dysplasia, Hutchinson Gilford progeria syndrome, restrictive dermopathy and autosomal recessive Charcot Marie Tooth type 2. The c.1930C > T (R644C) missense mutation has previously been reported in eight unrelated patients with variable features including left ventricular hypertrophy, limb girdle muscle weakness, dilated cardiomyopathy and atypical progeria. Here we report on the details of nine additional patients in eight families with this mutation. Patients 1 and 2 presented with lipodystrophy and insulin resistance, Patient 1 having in addition focal segmental glomerulosclerosis. Patient 3 presented with motor neuropathy, Patient 4 with arthrogryposis and dilated cardiomyopathy with left ventricular non-compaction, Patient 5 with severe scoliosis and contractures, Patient 6 with limb girdle weakness and Patient 7 with hepatic steatosis and insulin resistance. Patients 8 and 9 are brothers with proximal weakness and contractures. Nonpenetrance was observed frequently in first degree relatives. This report provides further evidence of the extreme phenotypic diversity and low penetrance associated with the R644C mutation. Possible explanations for these observations are discussed.
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PMID:Extreme phenotypic diversity and nonpenetrance in families with the LMNA gene mutation R644C. 1847 90

Mutations in the gene encoding the inner nuclear membrane proteins lamins A and C produce cardiac and skeletal muscle dysfunction referred to as Emery Dreifuss muscular dystrophy. Lamins A and C participate in the LINC complex that, along with the nesprin and SUN proteins, LInk the Nucleoskeleton with the Cytoskeleton. Nesprins 1 and 2 are giant spectrin-repeat containing proteins that have large and small forms. The nesprins contain a transmembrane anchor that tethers to the nuclear membrane followed by a short domain that resides within the lumen between the inner and outer nuclear membrane. Nesprin's luminal domain binds directly to SUN proteins. We generated mice where the C-terminus of nesprin-1 was deleted. This strategy produced a protein lacking the transmembrane and luminal domains that together are referred to as the KASH domain. Mice homozygous for this mutation exhibit lethality with approximately half dying at or near birth from respiratory failure. Surviving mice display hindlimb weakness and an abnormal gait. With increasing age, kyphoscoliosis, muscle pathology and cardiac conduction defects develop. The protein components of the LINC complex, including mutant nesprin-1alpha, lamin A/C and SUN2, are localized at the nuclear membrane in this model. However, the LINC components do not normally associate since coimmunoprecipitation experiments with SUN2 and nesprin reveal that mutant nesprin-1 protein no longer interacts with SUN2. These findings demonstrate the role of the LINC complex, and nesprin-1, in neuromuscular and cardiac disease.
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PMID:Disruption of nesprin-1 produces an Emery Dreifuss muscular dystrophy-like phenotype in mice. 1900

The pathogenesis of dilated cardiomyopathy in Emery- Dreifuss muscular dystrophy (EDMD) is still unknown. Autoimmune mechanisms have recently been taken into account. The aim of this investigation was to determine whether the level of circulating antibodies to heart proteins which were previously detected, correlates with disease progression. Troponin I was chosen as the target. Ten patients with EDMD and 10 age-matched normal controls were tested. An enzyme linked immunoassay (ELISA) technique was used to determine the possible relation between the level of anti-troponin I antibodies at diagnosis and at followup. Autoantibodies against troponin I were detected in all EDMD patients. At diagnosis the level was higher in the X-linked EDMD form (X-EDMD), as compared to the autosomal dominant form (AD-EDMD). At follow-up the elevated level of the autoantibodies persisted in all the EDMD cases. However, in the AD-EDMD form, the level was found to be significantly rising with disease progression, in the X-EDMD form, on the other hand, it was declining. No clear-cut relationship between the level of the circulating antibodies and cardiac symptomatology was present. Detection of anti-troponin I antibodies may provide a non-invasive marker of early stages of dilated cardiomyopathy in EDMD.
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PMID:Circulating autoantibodies to troponin I in Emery-Dreifuss muscular dystrophy. 1910 70

SUN-domain proteins interact directly with KASH-domain proteins to form protein complexes that connect the nucleus to every major cytoskeleton network. SUN-KASH protein complexes are also required for attaching centrosomes to the nuclear periphery and for alignment of homologous chromosomes, their pairing and recombination in meiosis. Other functions that require SUN-domain proteins include the regulation of apoptosis and maturation and survival of the germline. Laminopathic diseases affect the distribution of the SUN-KASH complexes, and mutations in KASH-domain proteins can cause Emery Dreifuss muscular dystrophy and recessive cerebellar ataxia. This review describes our current knowledge of the role of SUN-KASH domain protein complexes during development, meiosis and disease.
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PMID:SUN-domain and KASH-domain proteins during development, meiosis and disease. 1912 21

Bethlem myopathy and Ullrich congenital muscular dystrophy are part of the heterogeneous group of collagen VI-related muscle disorders. They are caused by mutations in collagen VI (ColVI) genes (COL6A1, COL6A2, and COL6A3) while LMNA mutations cause autosomal dominant Emery-Dreifuss muscular dystrophy. A muscular dystrophy pattern and contractures are found in all three conditions, making differential diagnosis difficult especially in young patients when cardiomyopathy is absent. We retrospectively assessed upper and lower limb muscle CT scans in 14 Bethlem/Ullrich patients and 13 Emery-Dreifuss patients with identified mutations. CT was able to differentiate Emery-Dreifuss muscular dystrophy from ColVI-related myopathies in selected thigh muscles and to a lesser extent calves muscles: rectus femoris fatty infiltration was selectively present in Bethlem/Ullrich patients while posterior thigh muscles infiltration was more prominently found in Emery-Dreifuss patients. A more severe fatty infiltration particularly in the leg posterior compartment was found in the Emery-Dreifuss group.
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PMID:Differentiating Emery-Dreifuss muscular dystrophy and collagen VI-related myopathies using a specific CT scanner pattern. 2057 34

The muscular dystrophies are a group of inherited diseases affecting skeletal muscle that also affect cardiac muscle. Cardiac involvement occurs as a degenerative process with fibrosis and fatty replacement of the myocardium. Electrophysiologists are asked to participate in the care of muscular dystrophy patients because of the risk of atrial arrhythmias, conduction disease, bradycardia, ventricular arrhythmias, and sudden death. Duchenne, Becker, and limb-girdle types 2C-2F and 2I are muscular dystrophies in which the development of a dilated cardiomyopathy is common. Arrhythmias and conduction disease occur after the development of the dilated cardiomyopathy. Patients are considered for pacemakers or implantable cardioverter-defibrillators on the basis of guidelines used for nonischemic cardiomyopathies. Myotonic types 1 and 2, Emery-Dreifuss, limb-girdle type 1B, and facioscapulohumeral muscular dystrophies present with conduction disease and associated arrhythmias and variably with a dilated cardiomyopathy. In myotonic type 1, Emery-Dreifuss, and limb-girdle type 1B muscular dystrophies, conduction abnormalities are frequent and often require pacing. Recent studies support the use of prophylactic implantable cardioverter-defibrillators rather than pacemakers. In all the muscular dystrophies, respiratory muscle involvement can impact quality and quantity of life and needs to be factored in when considering a prophylactic device.
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PMID:Arrhythmias in the muscular dystrophies. 2276 83

A-type lamins, generated from the LMNA gene by differential splicing, are type V intermediate filament proteins that polymerize to form part of the nuclear lamina, and are of considerable medical interest because missense mutations in LMNA give rise to a wide range of dystrophic and progeroid syndromes. Among these are dilated cardiomyopathy and two forms of muscular dystrophy (limb-girdle and Emery-Dreifuss), which are modeled in lmna (-/-) mice and mice engineered to express human disease mutations. Our recent study demonstrates that cardiac and skeletal muscle pathology in lmna (-/-) mice can be attributed to elevated MTORC1 signaling leading to impairment of autophagic flux. An accompanying paper from another laboratory shows similar impairments in mice engineered to express the LMNA H222P associated with dilated cardiomyopathy in humans and also in left ventricular tissue from human subjects. MTORC1 inhibition with rapalogs restores autophagic flux and improves cardiac function in both mouse models, and extends survival in the lmna (-/-) mice. These findings elaborate a potential treatment option for dilated cardiomyopathy and muscular dystrophy associated with LMNA mutation and supplement growing evidence linking impaired autophagy to human disease.
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PMID:Elevated MTORC1 signaling and impaired autophagy. 2306 82

Autosomal recessive Emery Dreifuss muscular dystrophy (AR-EDMD) is rare, with few reports in the medical literature. We describe the first cases of AR-EDMD and autosomal dominant familial partial lipodystrophy (FPLD) in the Hutterite population resulting from homozygous or heterozygous R482Q mutations in the lamin A/C gene (LMNA). Heterozygosity for LMNA R482Q mutation causes FPLD, which is associated with increased risk of hyperlipidemia and hypertension. The overall carrier frequency of the R482Q mutation in Dariusleut and Leherleut Hutterites in Alberta was found to be 1.45%. Homozygosity for this mutation has not been previously reported and here resulted in a combination of generalized lipodystrophy and EDMD. Knowledge that the LMNA R482Q mutation is present in this population is important for genetic counseling, surveillance, and management of the associated disorders.
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PMID:Homozygous lamin A/C familial lipodystrophy R482Q mutation in autosomal recessive Emery Dreifuss muscular dystrophy. 2331 86


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