Neuromuscular disorders : NMD
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Neuromuscul. Disord. · Nov 2006
Case ReportsOutpatient continuous inotrope infusion as an adjunct to heart failure therapy in Duchenne muscular dystrophy.
We report the use of continuous intravenous inotrope infusion as a palliative management strategy for the treatment of symptomatic, refractory, end stage cardiac dysfunction in patients with Duchenne muscular dystrophy. Milrinone and/or dobutamine administered by continuous intravenous infusion provided symptomatic and objective cardiovascular improvement up to 30 months in 3 individuals with Duchenne muscular dystrophy and severe dilated cardiomyopathy. Continuous inotrope infusion should be considered a practical treatment strategy for end stage cardiac dysfunction in Duchenne muscular dystrophy patients when cardiac transplantation is not a viable option.
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Neuromuscul. Disord. · Oct 2006
Comparative StudyA comparative analysis of collagen VI production in muscle, skin and fibroblasts from 14 Ullrich congenital muscular dystrophy patients with dominant and recessive COL6A mutations.
Ullrich congenital muscular dystrophy (UCMD) is caused by recessive and dominant mutations in COL6A genes. We have analysed collagen VI expression in 14 UCMD patients. Sequencing of COL6A genes had identified homozygous and heterozygous mutations in 12 cases. ⋯ Mutations affecting glycine substitutions in the conserved triple helical domain were common and all resulted in reduced collagen VI. This study expands the spectrum of collagen VI defects and shows that analysis of skin fibroblasts may be a useful technique for the detection of collagen VI abnormalities. In contrast, immunohistochemical analysis of skin biopsies may not always reveal an underlying collagen VI defect.
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Antisense oligonucleotide (AO) manipulation of pre-mRNA splicing of the dystrophin gene is showing promise in overcoming Duchenne muscular dystrophy (DMD)-causing mutations. To date, this approach has been limited to studies using animal models or cultured human muscle cells, and evidence that AOs can induce exon skipping in human muscle has yet to be shown. In this study, we used different AO analogues to induce exon skipping in muscle explants derived from normal and DMD human tissue. We propose that inducing exon skipping in human muscle explants is closer to in vivo conditions than cells in monolayer cultures, and may minimize the numbers of participants in Phase I clinical studies to demonstrate proof of principle of exon skipping in human muscle.
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Neuromuscul. Disord. · Aug 2006
Atypical presentations of spinal muscular atrophy type III (Kugelberg-Welander disease).
Spinal muscular atrophy type III (SMA III, Kugelberg-Welander disease) typically presents with symmetric proximal weakness, areflexia, and hypotonia. We present four children with spinal muscular atrophy type III who had atypical phenotypes. Three patients clearly had asymmetric weakness at presentation and two had upper motor neuron signs in the lower extremities (one patient had both features). ⋯ All patients had Gowers signs and two had pes planus. In patients with proximal muscle weakness the presence of asymmetrical weakness, upper motor neuron signs, or both, may be compatible with spinal muscular atrophy type III. The diagnosis of spinal muscular atrophy should be considered when other possibilities have been excluded.
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Neuromuscul. Disord. · Jun 2006
Case ReportsNovel slow-skeletal myosin (MYH7) mutation in the original myosin storage myopathy kindred.
Myosin storage myopathy (OMIM 608358), a congenital myopathy characterised by subsarcolemmal, hyaline-like accumulations of myosin in Type I muscle fibres, was first described by Cancilla and Colleagues in 1971 [Neurology 1971;21:579-585] in two siblings as 'familial myopathy with probable lysis of myofibrils in type I muscle fibres'. Two mutations in the slow skeletal myosin heavy chain gene (MYH7) have recently been associated with the disease in other families. We have identified a novel heterozygous Leu1793Pro mutation in MYH7 in DNA from paraffin sections of one of the original siblings. This historical molecular analysis confirms the original cases had myosin storage myopathy.