Myology research highlights
RSS feedTubular aggregate myopathy resulting from dominant mutations in ORAI1
The store-operated Ca2+ release-activated Ca2+ (CRAC) channel is activated by diminished luminal Ca2+ levels in the endoplasmic reticulum and sarcoplasmic reticulum, and constitutes one of the major Ca2+ entry pathways in various tissues. Tubular aggregates are abnormal structures in the skeletal muscle, and although their mechanism of formation has not been clarified, altered Ca2+ homeostasis … [Read more]
Leiomodin-3 dysfunction results in thin filament disorganization and nemaline myopathy
Nemaline myopathy (NM) is a genetic muscle disorder characterized by muscle dysfunction and electron-dense protein accumulations (nemaline bodies) in myofibers. Pathogenic mutations have been described in 9 genes to date, but the genetic basis remains unknown in many cases. Here, using an approach that combined whole-exome sequencing (WES) and Sanger sequencing, the authors identified homozygous … [Read more]
Effect of antioxidants on FSHD muscle function
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease characterized by progressive weakness and atrophy of specific skeletal muscles. As growing evidence suggests that oxidative stress may contribute to FSHD pathology, antioxidants that might modulate or delay oxidative insults could help maintain FSHD muscle function. The main objective of this study was to test whether … [Read more]
Drisapersen DEMAND II study: Promising safety and efficacy results
Duchenne muscular dystrophy is caused by dystrophin deficiency and muscle deterioration and preferentially affects boys. Antisense-oligonucleotide-induced exon skipping allows synthesis of partially functional dystrophin. This exploratory, double-blind, placebo-controlled study investigated the efficacy and safety of drisapersen, a 2′-O-methyl-phosphorothioate antisense oligonucleotide, given for 48 weeks. Fifty three male patients (≥5 years of age; time to rise … [Read more]
Variants in the dystrophin gene are linked to cognitive function
This study investigated whether single-nucleotide dystrophin gene (DMD) variants are associated with variability in cognitive functions in healthy populations. The study included 1240 participants from the Erasmus Rucphen family (ERF) study and 1464 individuals from the Rotterdam Study (RS). The participants whose exomes were sequenced and who were assessed for various cognitive traits were included … [Read more]
A new muscle glycogen storage disease associated with Glycogenin-1 deficiency
This study describes a slowly progressive myopathy in seven unrelated adult patients with storage of polyglucosan in muscle fibers. Genetic investigation revealed homozygous or compound heterozygous deleterious variants in the glycogenin-1 gene (GYG1). Most patients showed depletion of glycogenin-1 in skeletal muscle whereas one showed presence of glycogenin-1 lacking the C-terminal that normally binds glycogen … [Read more]
Inhibition of JAK-STAT signaling stimulates adult satellite cell function
Diminished regenerative capacity of skeletal muscle occurs during adulthood. Here, the authors identified a reduction in the intrinsic capacity of mouse adult satellite cells to contribute to muscle regeneration and repopulation of the niche. Gene expression analysis identified higher expression of JAK-STAT signaling targets in 3-week-old relative to 18-month-old mice. Knockdown of Jak2 or Stat3 … [Read more]
Charcot-Marie-Tooth disease resulting from a COX6A1 mutation
Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy characterized by clinical and genetic heterogeneity. Although more than 30 loci harboring CMT-causing mutations have been identified, many other genes still remain to be discovered for many affected individuals. For two consanguineous families with CMT (axonal and mixed phenotypes), a parametric linkage analysis using genome-wide SNP … [Read more]
Morpholino antisense oligonucleotides: a new molecular target for SMA
Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by the loss of Survival Motor Neuron-1 (SMN1). In all SMA patients, a nearly identical copy gene called SMN2 is present, which produces low levels of functional protein owing to an alternative splicing event. To prevent exon-skipping, the authors targeted an intronic repressor, Element1 (E1), located … [Read more]
Generation of a mouse model containing an X-Linked DUX4 transgene
Facioscapulohumeral muscular dystrophy (FSHD) is an enigmatic disease associated with epigenetic alterations in the subtelomeric heterochromatin of the D4Z4 macrosatellite repeat. Each repeat unit encodes DUX4, a gene that is normally silent in most tissues. Besides muscular loss, most patients suffer retinal vascular telangiectasias. To generate an animal model, a doxycycline-inducible transgene encoding DUX4 and … [Read more]
