Myology research highlights

Centronuclear myopathies (CNM) are rare inherited disorders characterized by nuclei placed in rows in the central part of the muscle fibres. Three CNM-causing genes have been identified, with MTM1 mutations provoking X-linked myotubular myopathy, DNM2 mutations provoking autosomal dominant (AD) CNM, and BIN1 mutations provoking autosomal recessive (AR) CNM. In this retrospective monocentric study, the … [Read more]

Dilated cardiomyopathy (DCM) is a leading cause of chronic morbidity and mortality in muscular dystrophy (MD) patients. Current pharmacological treatments are not yet able to counteract chronic myocardial wastage, thus novel therapies are being intensely explored. MicroRNAs have been implicated as fine regulators of cardiomyopathic progression. Previously, miR-669a downregulation has been linked to the severe … [Read more]

Outcome measures for clinical trials in neuromuscular diseases are typically based on physical assessments, which are dependent on patient effort, combine the effort of different muscle groups, and may not be sensitive to progression over short trial periods in slow-progressing diseases. In this study, the authors hypothesised that quantitative fat imaging by MRI (Dixon technique) … [Read more]

Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder, with a fairly homogeneous clinical phenotype (progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, and depressed tendon reflexes). With more than 40 genes implicated, an update of the present and rather confusing classification of CMT is needed. Over the last few years, … [Read more]

Myotonic dystrophy type 1 (DM1) is an RNA-mediated disorder caused by a non-coding CTG repeat expansion that, in particular, provokes functional alteration of CUG-binding proteins. As a consequence, several genes with misregulated alternative splicing have been linked to clinical symptoms. In search for additional molecular mechanisms that would trigger functional defects in DM1, the authors … [Read more]

Congenital myopathies are heterogeneous inherited diseases of muscle characterized by a range of distinctive histologic abnormalities. Herein, the authors have studied a consanguineous family with congenital myopathy. Genome-wide linkage analysis and whole-exome sequencing identified a homozygous nonsense mutation in 3-hydroxyacyl-CoA dehydratase 1 (HACD1) in affected individuals. The mutation results in non-sense mediated decay of the … [Read more]

In prior open-label studies, eteplirsen, a phosphorodiamidate morpholino oligomer (PMO), enabled dystrophin production in Duchenne muscular dystrophy (DMD) with genetic mutations amenable to skipping exon 51. The present study used a double-blind placebo-controlled protocol to test eteplirsen’s ability to induce dystrophin production and improve distance walked on the 6-minute walk test (6MWT). DMD boys aged … [Read more]

An international Clinical Outcomes Group consisting of clinicians, scientists, patient advocacy groups, and industries identified a need for a scale to measure motor performance of the upper limb. This study reports the steps leading to the development of the Performance of the Upper Limb (PUL), a tool specifically designed for assessing upper limb function in … [Read more]

In this study, the authors aimed to develop RNA splicing biomarkers of disease severity and therapeutic response in myotonic dystrophy type 1 (DM1) and type 2 (DM2). In a discovery cohort, they used microarrays to perform global analysis of alternative splicing in DM1 and DM2. The newly identified splicing changes were combined with previous data … [Read more]

Myotonic dystrophy type 1 (DM1) is an inherited dominant muscular dystrophy caused by expanded CTG•CAG triplet repeats in the 3′ UTR of the DMPK1 gene, which produces a toxic gain-of-function CUG RNA. It has been shown that the severity of disease symptoms, age of onset and progression are related to the length of the triplet … [Read more]