1/234. A heterozygous splice site mutation in COL6A1 leading to an in-frame deletion of the alpha1(VI) collagen chain in an italian family affected by bethlem myopathy.Bethlem myopathy is a mild neuromuscular disorder with proximal muscular weakness and early flexion contractures. It is an autosomal dominant disease due to mutations in type VI collagen genes. We found a T-->C substitution at the 2 position of COL6A1 intron 14 in a family, leading to skipping of exon 14 and an in-frame deletion of 18 amino acids in the triple-helical domain of the alpha1(VI) collagen chain. The deletion included a cysteine residue believed to be involved in the assembly of type VI collagen dimers intracellularly, prior to the protein secretion. Analysis of the affected fibroblasts showed that the shortened alpha1(VI) collagen chains were synthesized but not secreted by the cells and that the amount of type VI collagen microfibrils deposited by the cells was reduced. The results suggest that the clinical phenotype is due to a reduction in the level of type VI collagen in the extracellular matrix.- - - - - - - - - - ranking = 1keywords = myopathy (Clic here for more details about this article) |
2/234. A case of McLeod syndrome with chronic renal failure.A 50-year-old man with the rare McLeod syndrome, associated with glomerular lesion to the end stage of chronic renal failure and death, is reported. McLeod syndrome is an X-linked recessive disorder on the basis of abnormal expression of the Kell blood group antigens and absence of erythrocyte surface Kx antigen. Most often the clinical and pathological findings are retinitis pigmentosa to blindness, progressive chronic neuropathy, cortical atrophy, dilated cardiomyopathy, and glomerular lesion with chronic renal failure. Among the laboratory parameters the most important are very low level of cholesterol and triglycerides, then various numbers of acanthocytes in peripheral blood smears and sometimes in urine (as in our case).- - - - - - - - - - ranking = 0.2keywords = myopathy (Clic here for more details about this article) |
3/234. Proximal myotonic myopathy (PROMM) presenting as myotonia during pregnancy.Proximal myotonic myopathy is a recently described autosomal dominant condition characterized by proximal myopathy, cataracts, intermittent myotonia, and myalgia. We report a further family with this condition. The proband and her two sisters presented with myotonia during pregnancy which resolved after each delivery. Two sisters experienced myalgia between each pregnancy. This relationship between pregnancy and symptom exacerbation suggests an intriguing hormonal influence in PROMM.- - - - - - - - - - ranking = 1.2keywords = myopathy (Clic here for more details about this article) |
4/234. A novel de novo mutation in the triple helix of the COL6A3 gene in a two-generation Italian family affected by Bethlem myopathy. A diagnostic approach in the mutations' screening of type VI collagen.Bethlem myopathy is an autosomal dominant inherited disease producing a mild neuromuscular disorder, characterized mainly by muscular weakness and multiple joint contractures. Bethlem myopathy is caused by mutations in one of the three chains of collagen type vi. Here we report the clinical description and the molecular characterization of the defect in a two-generation Italian family in which a Gly-->Arg substitution disrupts the triple helix structure of the alpha 3 chain of collagen type vi, an ubiquitous glycoprotein of the extracellular matrix. In this family the identification of the mutation also allowed one to exclude the disease in the grandfather. It is noteworthy that the father of the proband carries a de novo mutation, the first described for Bethlem myopathy.- - - - - - - - - - ranking = 1.4keywords = myopathy (Clic here for more details about this article) |
5/234. Autonomic failure and proximal skeletal myopathy in a patient with primary Sjogren syndrome.Autonomic failure and proximal skeletal myopathy are rare features of the Sjogren syndrome (SS). We describe a 51-year-old woman with primary SS who had development of esophageal dysmotility, urinary retention, severe orthostatism, and skeletal myopathy during a 3-month period after the diagnosis of SS. Her symptoms and signs responded well to corticosteroid therapy. Although dysfunction of the peripheral nervous system has a prevalence rate of 20% in patients with SS, most commonly the nerve dysfunction is a sensory deficit, and autonomic neuropathy is less frequent. Autonomic neuropathy due to SS may be underreported. The cause of our patient's myopathy remains undetermined. We speculate that the myopathy was due to either a form of polymyositis or an immune-mediated neuropathy with muscle involvement.- - - - - - - - - - ranking = 1.6keywords = myopathy (Clic here for more details about this article) |
6/234. Bethlem myopathy and engineered collagen VI triple helical deletions prevent intracellular multimer assembly and protein secretion.Mutations in the genes that code for collagen VI subunits, COL6A1, COL6A2, and COL6A3, are the cause of the autosomal dominant disorder, Bethlem myopathy. Although three different collagen VI structural mutations have previously been reported, the effect of these mutations on collagen VI assembly, structure, and function is currently unknown. We have characterized a new Bethlem myopathy mutation that results in skipping of COL6A1 exon 14 during pre-mRNA splicing and the deletion of 18 amino acids from the triple helical domain of the alpha1(VI) chain. Sequencing of genomic dna identified a G to A transition in the 1 position of the splice donor site of intron 14 in one allele. The mutant alpha1(VI) chains associated intracellularly with alpha2(VI) and alpha3(VI) to form disulfide-bonded monomers, but further assembly into dimers and tetramers was prevented, and molecules containing the mutant chain were not secreted. This triple helical deletion thus resulted in production of half the normal amount of collagen VI. To further explore the biosynthetic consequences of collagen VI triple helical deletions, an alpha3(VI) cDNA expression construct containing a 202-amino acid deletion within the triple helix was produced and stably expressed in SaOS-2 cells. The transfected mutant alpha3(VI) chains associated with endogenous alpha1(VI) and alpha2(VI) to form collagen VI monomers, but dimers and tetramers did not form and the mutant-containing molecules were not secreted. Thus, deletions within the triple helical region of both the alpha1(VI) and alpha3(VI) chains can prevent intracellular dimer and tetramer assembly and secretion. These results provide the first evidence of the biosynthetic consequences of structural collagen VI mutations and suggest that functional protein haploinsufficiency may be a common pathogenic mechanism in Bethlem myopathy.- - - - - - - - - - ranking = 1.4keywords = myopathy (Clic here for more details about this article) |
7/234. Atrial standstill in a case of Kugelberg-Welander syndrome with cardiac involvement: an electrophysiologic study.A patient with Kugelberg-Welander syndrome associated with junctional rhythm and restrictive cardiomyopathy is presented. An electrophysiologic study was performed. Persistent atrial standstill was demonstrated by detailed right atrium and coronary sinus mapping and failure of capture of both right atrium and coronary sinus pacing. A prolonged junctional recovery time, normal HV interval and normal pacing threshold of the right ventricle were also noted. The patient was successfully treated with cardiac pacing and diuretics.- - - - - - - - - - ranking = 0.2keywords = myopathy (Clic here for more details about this article) |
8/234. A case of McLeod syndrome with unusually severe myopathy.A 51-year-old man developed weakness and muscle atrophy in the legs at the age of 41, later followed by choreiform involuntary movements. Neurological and laboratory examinations revealed severe muscle weakness and atrophy, and areflexia in all the extremities, acanthocytosis and an elevated serum creatine kinase level. Together with these findings, the weak expression of Kell blood group antigens and the absence of the Kx antigen led to a definite diagnosis of McLeod syndrome for his condition. brain magnetic resonance imaging revealed marked atrophy of the head of the caudate nuclei. Although immunocytochemical analysis of dystrophin in muscle specimens from our patient revealed normal staining, we found prominent fiber size variability, central nuclei, and connective tissue proliferation as well as necrotic and regenerating fibers, which are as a whole compatible with the myopathology of muscular dystrophy. Moreover, muscle computerized tomography of the lower extremities revealed the 'selectivity pattern' characteristically reported in muscular dystrophies including Duchenne type muscular dystrophy. The muscular symptoms and pathology in McLeod syndrome have been reported to be mild, but the present case clearly shows that the muscular features in this condition may be much more severe than previously thought.- - - - - - - - - - ranking = 0.87432269831678keywords = myopathy, muscular dystrophy, dystrophy (Clic here for more details about this article) |
9/234. Fatal infantile cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene.Mammalian cytochrome c oxidase (COX) catalyses the transfer of reducing equivalents from cytochrome c to molecular oxygen and pumps protons across the inner mitochondrial membrane. Mitochondrial dna (mtDNA) encodes three COX subunits (I-III) and nuclear dna (nDNA) encodes ten. In addition, ancillary proteins are required for the correct assembly and function of COX (refs 2, 3, 4, 5, 6). Although pathogenic mutations in mtDNA-encoded COX subunits have been described, no mutations in the nDNA-encoded subunits have been uncovered in any mendelian-inherited COX deficiency disorder. In yeast, two related COX assembly genes, SCO1 and SCO2 (for synthesis of cytochrome c oxidase), enable subunits I and II to be incorporated into the holoprotein. Here we have identified mutations in the human homologue, SCO2, in three unrelated infants with a newly recognized fatal cardioencephalomyopathy and COX deficiency. Immunohistochemical studies implied that the enzymatic deficiency, which was most severe in cardiac and skeletal muscle, was due to the loss of mtDNA-encoded COX subunits. The clinical phenotype caused by mutations in human SCO2 differs from that caused by mutations in SURF1, the only other known COX assembly gene associated with a human disease, Leigh syndrome.- - - - - - - - - - ranking = 1keywords = myopathy (Clic here for more details about this article) |
10/234. Neuromuscular syndrome associated with the 3291T-->C mutation of mitochondrial dna: a second case.A mutation was found in an Italian child affecting the gene encoding the mitochondrial transfer rna for leucine (codon UUR). This mutation (3291T-->C) had previously been reported in a single Japanese patient. In contrast with the original patient, who suffered from early-onset mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), our patient presented an apparently isolated mild myopathy. Mutational analysis in the proband and her family showed that the mutation was heteroplasmic, and that its relative amount was positively correlated with the severity of the phenotype. These findings lead to the definitive confirmation that the 3291T-->C is indeed pathogenic. As commonly found in mitochondrial-dna related disorders, also for this mutation different clinical manifestations can be associated with the same genetic abnormality.- - - - - - - - - - ranking = 0.4keywords = myopathy (Clic here for more details about this article) |
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