Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We had a case of Emery-Dreifuss muscular dystrophy (EDMD) in an 18-year-old woman who underwent endovascular therapy for a cardioembolic stroke. At 5 years old, she showed a high creatine kinase level and atrial fibrillation on electrocardiography in our hospital. Finally, she was diagnosed as having EDMD by genetic screening that revealed mutations in the LMNA gene (c.810+1G>T). Before this event, she received no medications. At 18 years old, she was admitted to our hospital>8 hours after the onset of sudden consciousness disturbance. Neurological examination on admission revealed consciousness disturbance and right hemiplegia. Magnetic resonance imaging revealed a cerebral infarction in the left insular cortex and putamen with left internal carotid artery occlusion. We performed endovascular therapy and completely recanalized her left internal carotid artery. Thereafter, her neurological symptoms improved. She was subsequently transferred to a rehabilitation hospital. EDMD is a rare genetic muscular disease that mainly presents with contractures, weakness, and cardiac conduction abnormalities. Although patients with EDMD are young with low CHADS2 score, they have a disease-specific cardiovascular pathogenesis caused by a fatal risk factor. Therefore, we consider anticoagulant therapy necessary to prevent thrombotic events, even if the CHADS2 score is low, in patients with EDMD.
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PMID:A Young Patient with Emery-Dreifuss Muscular Dystrophy Treated with Endovascular Therapy for Cardioembolic Stroke: A Case Report. 3019 44

LMNA linked-Emery-Dreifuss muscular dystrophy (EDMD2) is a rare disease characterized by muscle weakness, muscle wasting, and cardiomyopathy with conduction defects. The mutated protein lamin A/C binds several nuclear envelope components including the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex and the inner nuclear membrane protein Samp1 (Spindle Associated Membrane Protein 1). Considering that Samp1 is upregulated during muscle cell differentiation and it is involved in nuclear movement, we hypothesized that it could be part of the protein platform formed by LINC proteins and prelamin A at the myotube nuclear envelope and, as previously demonstrated for those proteins, could be affected in EDMD2. Our results show that Samp1 is uniformly distributed at the nuclear periphery of normal human myotubes and committed myoblasts, but its anchorage at the nuclear poles is related to the presence of farnesylated prelamin A and it is disrupted by the loss of prelamin A farnesylation. Moreover, Samp1 is absent from the nuclear poles in EDMD2 myotubes, which shows that LMNA mutations associated with muscular dystrophy, due to reduced prelamin A levels in muscle cell nuclei, impair Samp1 anchorage. Conversely, SUN1 pathogenetic mutations do not alter Samp1 localization in myotubes, which suggests that Samp1 lies upstream of SUN1 in nuclear envelope protein complexes. The hypothesis that Samp1 is part of the protein platform that regulates microtubule nucleation from the myotube nuclear envelope in concert with pericentrin and LINC components warrants future investigation. As a whole, our data identify Samp1 as a new contributor to EDMD2 pathogenesis and our data are relevant to the understanding of nuclear clustering occurring in laminopathic muscle.
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PMID:Samp1 Mislocalization in Emery-Dreifuss Muscular Dystrophy. 3032 51

This article reports a case of limb-girdle muscular dystrophy type 1B (LGMD1B) caused by a novel splicing heterozygous mutation in the LMNA gene. The proband presented with progressive aggravation of weakness in walking. There was no atrophy of the scapular muscles and the lower-extremity proximal muscles, with normal muscle tension of the extremities, grade 4 muscle strength in the upper and lower extremities, and positive Gower sign. The level of creatine kinase was 779 U/L. Muscle hematoxylin-eosin staining showed muscular dystrophy, and there was no significant reduction in the expression of Lamin A protein. Second-generation sequencing revealed a novel splicing heterozygous mutation, c.810+2T>C, in the LMNA gene, while this locus was normal in his parents. GERP++RS software predicted that the mutation site was highly conservative. Human Splice Finder and Spliceman software predicted that the mutation might be a pathogenic mutation. ExPASy software predicted that the new amino acid sequence became shorter. There were two sequences of mRNA in the patient's muscle: one was the normal sequence, which accounted for 92.2%; the other was partial intron 4 retention, which was the abnormal splice variant accounting for 7.8%. LGMD1B is a type of autosomal dominant inherited myopathy caused by a mutation in the LMNA gene located on the autosomal 1q22. This study extends the mutation spectrum of the LMNA gene and provides help to the diagnosis of LGMD1B.
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PMID:[Clinical and genetic features of limb-girdle muscular dystrophy type 1B: a case report]. 3057 90

A-type lamins gene (LMNA) mutations cause an autosomal dominant inherited form of Emery-Dreifuss muscular dystrophy (EDMD). EDMD is characterized by slowly progressive muscle weakness and wasting and dilated cardiomyopathy, often leading to heart failure-related disability. EDMD is highly penetrant with poor prognosis and there is currently no specific therapy available. Clinical variability ranges from early onset with severe presentation in childhood to late onset with slow progression in adulthood. Genetic background is a well-known factor that significantly affects phenotype in several mouse models of human diseases. This phenotypic variability is attributed, at least in part, to genetic modifiers that regulate the disease process. To characterize the phenotype of A-type lamins mutation on different genetic background, we created and phenotyped C57BL/6JRj-Lmna H222P/H222P mice (C57 Lmna p.H222P) and compared them with the 129S2/SvPasCrl-Lmna H222P/H222P mice (129 Lmna p.H222P). These mouse strains were compared with their respective control strains at multiple time points between 3 and 10 months of age. Both contractile and electrical cardiac muscle functions, as well as survival were characterized. We found that 129 Lmna p.H222P mice showed significantly reduced body weight and reduced cardiac function earlier than in the C57 Lmna p.H222P mice. We also revealed that only 129 Lmna p.H222P mice developed heart arrhythmias. The 129 Lmna p.H222P model with an earlier onset and more pronounced cardiac phenotype may be more useful for evaluating therapies that target cardiac muscle function, and heart arrhythmias.
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PMID:Effect of genetic background on the cardiac phenotype in a mouse model of Emery-Dreifuss muscular dystrophy. 3134 69

The LMNA gene is associated to a huge broad of phenotypes, including congenital Emery-Dreifuss muscular dystrophy and late-onset LMNA-related muscular dystrophy. In these forms, muscle weakness, contractures, and cardiac impairment are common. In an autosomal dominant pedigree including 5 affected patients, NGS molecular analysis performed in 6 relatives identifies the heterozygous c.1129C>T p.Arg377Cys variant in the exon 6 of the LMNA gene in three of them. Clinical, laboratorial, imaging investigation of these affected patients showed a significant clinical variability: the father presented subclinical imaging muscular dystrophy masqueraded as radiculopathy. One of his sons presented cardiac arrhythmia, muscular weakness, elbow contractures, and intranuclear pseudoinclusions on muscle biopsy. A second son presented only decreased tendon reflexes. Two other brothers presenting myalgia and cramps were not carriers of the same mutation in the LMNA gene. Early diagnosis, considering these variable phenotype and genotype, is important for genetic counseling, as well as cardiac, and rehabilitation management.
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PMID:LMNA-Related Muscular Dystrophy with Clinical Intrafamilial Variability. 3141 Jun 51

Respiratory muscle weakness is often complicated in patients with heart failure. Its presence further worsens the clinical course of heart failure. However, the effect and appropriate method of inspiratory muscle training has not previously been elucidated. A 55-year-old man with dilated cardiomyopathy was admitted for intractable heart failure. His heart failure was dependent on catecholamine infusion and the implantation of left ventricular assist device was planned. He also had suffered from some muscle weakness, which was later diagnosed as lamin dystrophy due to mutation of LMNA c.G97T E33X. Preoperatively we started aerobic rehabilitation with inspiratory muscle training. Before training, inspiratory and expiratory muscle strength was significantly reduced and exercise capacity was decreased. The load of inspiratory training could be gradually increased along the result of regular evaluation of respiratory muscle strength. During 8 weeks of training, there was no worsening of heart failure and no significant events related to arrhythmia. After training, respiratory muscle strength and exercise capacity were improved significantly. <Learning objective: Inspiratory muscle training was effective and safe in a patient with intractable heart failure, which was complicated by skeletal muscle myopathy due to lamin-related muscular dystrophy.>.
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PMID:Inspiratory muscle training for advanced heart failure with lamin-related muscular dystrophy. 3176 41

Emery-Dreifuss muscular dystrophy (EDMD) is a rare muscular dystrophy, but is particularly important to diagnose due to frequent life-threatening cardiac complications. EDMD classically presents with muscle weakness, early contractures, cardiac conduction abnormalities and cardiomyopathy, although the presence and severity of these manifestations vary by subtype and individual. Associated genes include EMD, LMNA, SYNE1, SYNE2, FHL1, TMEM43, SUN1, SUN2, and TTN, encoding emerin, lamin A/C, nesprin-1, nesprin-2, FHL1, LUMA, SUN1, SUN2, and titin, respectively. The Online Mendelian Inheritance in Man database recognizes subtypes 1 through 7, which captures most but not all of the associated genes. Genetic diagnosis is essential whenever available, but traditional diagnostic tools can help steer the evaluation toward EDMD and assist with interpretation of equivocal genetic test results. Management is primarily supportive, but it is important to monitor patients closely, especially for potential cardiac complications. There is a high potential for progress in the treatment of EDMD in the coming years.
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PMID:Emery-Dreifuss muscular dystrophy. 3184 Feb 75

A 23-year-old man had progressive muscle weakness and Emery-Dreifuss muscular dystrophy (EDMD) due to a LMNA (lamin A/C) mutation. Congestive heart failure diagnosed at 19 years of age. Maximal drug treatment/cardiac resynchronization failed to improve the cardiac function. He was therefore hospitalized due to heart failure. Despite extracorporeal membrane oxygenation, he developed severe right heart dysfunction and died (multiple organ failure). A cardiac lesion's presence determines the prognosis of EDMD. While there are many arrhythmia reports, few reports on heart failure (particularly severe heart failure requiring cardiac transplantation) have been published. Right heart function monitoring and early ventricular-assist device use plus right heart support considering heart transplantation are important.
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PMID:Refractory Right Ventricular Failure in a Patient with Emery-Dreifuss Muscular Dystrophy. 3207 78


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