Myology research highlights
RSS feedPotential of iPSC-derived neural stem cells in motor neuron disorders
Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a motor neuron disease caused by mutations in the IGHMBP2 gene, without a cure. Here, the authors demonstrate that neural stem cells (NSCs) from human-induced pluripotent stem cells (iPSCs) have therapeutic potential in the context of SMARD1. They show that upon transplantation NSCs can appropriately … [Read more]
Lambert-Eaton Myasthenic Syndrome study shows promising results
Firdapse (amifampridine phosphate) a leading drug from Catalyst Pharmaceutical Partners Inc, has demonstrated superior results compared to placebo for treating symptoms associated with the rare autoimmune disorder Lambert-Eaton Myasthenic Syndrome (LEMS). LEMS is a neuromuscular disease causing progressive muscle weakness, and it is often associated with cancer. All patients in the phase III randomized “withdrawal” … [Read more]
PYGM expression analysis in white blood cells: A complementary tool for diagnosing McArdle disease?
McArdle disease is caused by an inherited deficiency of the enzyme myophosphorylase, resulting in exercise intolerance from childhood and acute crises of early fatigue and contractures. In severe cases, these manifestations can be accompanied by rhabdomyolysis, myoglobinuria, and fatal renal failure. Diagnosis of McArdle disease is based on clinical diagnostic tests, together with an absence … [Read more]
Tubular 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]
Expanding the clinical and histological phenotype of ACTA1 disease
Variants in ACTA1, which encodes α-skeletal actin, cause several congenital myopathies, most commonly nemaline myopathy. Autosomal recessive variants comprise approximately 10% of ACTA1 myopathy. All recessive variants reported to date have resulted in loss of skeletal α-actin expression from muscle and severe weakness from birth. Targeted next-generation sequencing in two brothers with congenital muscular dystrophy … [Read more]
Junctophilin-1 is a modifier gene of GDAP1-related Charcot-Marie-Tooth disease
Mutations in the GDAP1 gene cause different forms of Charcot-Marie-Tooth (CMT) disease, and the primary clinical expression of this disease is markedly variable in the dominant inheritance form (CMT type 2K; CMT2K), in which carriers of the GDAP1 p.R120W mutation can display a wide range of clinical severity. Here, the authors investigated the junctophilin-1 (JPH1) … [Read more]
Vacuolar myopathy due to a mutation in the CASQ1 gene
A missense mutation in the calsequestrin-1 gene (CASQ1) was found in a group of patients with a myopathy characterized by weakness, fatigue and the presence of large vacuoles containing characteristic inclusions resulting from the aggregation of sarcoplasmic reticulum (SR) proteins. The mutation affects a conserved aspartic acid in position 244 (p.Asp244Gly) located in one of … [Read more]
Identification of a novel, inherited neuromuscular disease
Synaptotagmin 2 is a synaptic vesicle protein that functions as a calcium sensor for neurotransmission but has not been previously associated with human disease. Via whole-exome sequencing, heterozygous missense mutations in the C2B calcium-binding domain of the gene encoding Synaptotagmin 2 were identified in two multigenerational families presenting with peripheral motor neuron syndromes. An essential … [Read more]
Incidence and prevalence of FSHD in the Netherlands
In this study, the authors aimed to determine the incidence and prevalence of facioscapulohumeral muscular dystrophy (FSHD) in the Netherlands. They used 3-source capture-recapture methodology, to estimate the total yearly number of newly found symptomatic individuals with FSHD, including those not registered in any of the 3 sources. To this end, symptomatic individuals with FSHD … [Read more]
