Blog Archives

Pompe disease is a neuromuscular disease resulting from deficiency in acid α-glucosidase (GAA), results in cardiac, skeletal muscle, and central nervous system (CNS) pathology. Enzyme replacement therapy (ERT) has been shown to partially correct cardiac and skeletal muscle dysfunction. However, ERT does not cross the blood-brain barrier and progressive CNS pathology ensues. Here, the authors … [Read more]

Myotonic dystrophy type 1 is an autosomal dominant condition caused by a trinucleotide CTG repeat expansion in the 3′ untranslated region of the dystrophia myotonica protein kinase gene. The phenotypic features of myopathic facies, generalized weakness, and myotonia are thought to be dependent on repeat number, with larger expansions generally leading to earlier and/or more … [Read more]

Idiopathic myopathies are a group of acquired muscular diseases considered as autoimmune disorders. Characteristic histopathologic features allow the classification into myositis (polymyositis, dermatomyositis, and inclusion body myositis) and immune-mediated necrotising myopathies. But overlapping histological features may be observed between different idiopathic myopathies and even between acquired and genetic muscular diseases. In the group of idiopathic … [Read more]

Laminopathies, caused by mutations in the LMNA gene encoding the nuclear envelope proteins lamins A and C, represent a diverse group of diseases that include Emery-Dreifuss muscular dystrophy (EDMD), dilated cardiomyopathy (DCM), limb-girdle muscular dystrophy, and Hutchison-Gilford progeria syndrome. Most LMNA mutations affect skeletal and cardiac muscle by mechanisms that remain incompletely understood. Loss of … [Read more]

Glucocorticoid (GC) therapy in Duchenne muscular dystrophy (DMD) has altered disease progression, necessitating contemporary natural history studies. In this study, the Cooperative Neuromuscular Research Group (CINRG) DMD Natural History Study (DMD-NHS) enrolled 340 DMD males, aged 2-28 years to carry out a comprehensive battery of measures. A novel composite functional “milestone” scale showed clinically meaningful … [Read more]

Of the seven autosomal dominant genetically distinct forms of LGMD so far described, in only four the causative gene has been identified (LGMD1A-1D). Herein the authors describe clinical, histopathological and muscle MRI features of a large Italo-Spanish kindred with LGMD1F presenting proximal-limb and axial muscle weakness. Complete clinical data were obtained and the progression of … [Read more]

Dysferlinopathy refers to a group of autosomal recessive muscular dystrophies due to mutations in the dysferlin gene causing deficiency of a membrane-bound protein crucially involved in plasma membrane repair. The condition is characterized by marked clinical heterogeneity, the different phenotypes/modes of presentation being unrelated to the genotype. For unknown reasons, patients are often remarkably active … [Read more]

Spinal muscular atrophy (SMA) is caused by loss of the Survival Motor Neuron 1 (SMN1) gene, resulting in reduced SMN protein. Humans possess the additional SMN2 gene (or genes) that does produce low level of full length SMN, but cannot adequately compensate for loss of SMN1 due to aberrant splicing. The majority of SMN2 gene … [Read more]

Muscular dystrophies are a class of disorders that cause progressive muscle wasting. A major hurdle for discovering treatments for the muscular dystrophies is a lack of reliable assays to monitor disease progression in animal models. We have developed a novel mouse model to assess disease activity noninvasively in mice with muscular dystrophies. These mice express … [Read more]

Mutations in the skeletal muscle ryanodine receptor (RYR1) gene are a common cause of neuromuscular disease, ranging from various congenital myopathies to the malignant hyperthermia (MH) susceptibility trait without associated weakness. The RYR1 gene was sequenced in 39 unrelated families with rhabdomyolysis and/or exertional myalgia, frequent presentations in the neuromuscular clinic that often remain unexplained … [Read more]