Blog Archives
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]
Validation of recombinant AAV for exon skipping in DMD
Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disorder caused by mutations in the dystrophin gene, without curative treatment yet available. This study is the first to provide the overall safety profile and therapeutic dose of a recombinant adeno-associated virus vector, serotype 8 (rAAV8) carrying a modified U7snRNA sequence. This sequence promotes exon skipping to … [Read more]
MRI of lower extremity skeletal muscles in DMD
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder that results in functional deficits. However, these functional declines can often not be quantified in clinical trials for DMD until after age 7. In this study, the authors hypothesized that 1H2O T2 derived using 1H-MRS and MRI-T2 will be sensitive to muscle involvement at a young … [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]
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]
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]
Motor and cognitive delay in DMD
This study examined the relationship between delay in the age of first independent walking and cognitive impairment in boys with Duchenne muscular dystrophy (DMD) to assess how age of diagnosis might be improved. The records of 179 boys with DMD evaluated by the senior author between 1989 and June 2012 were reviewed. Delay in walking … [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]
Save the date! MYOLOGY 2016 – Fifth International Congress of Myology
After Lille in 2011, AFM-Telethon is organizing its Fifth International Congress of Myology in Lyon, from 14th till 18th March 2016 Held for the first time in 2000, MYOLOGY has become a unique opportunity for international experts in the field to exchange and confront the emerging therapeutic approaches, but also to share the first clinical … [Read more]
Identification of prednisone responsive biomarkers
Prednisone is often used for the treatment of autoimmune and inflammatory diseases but patients suffer from variable therapeutic responses and significant adverse effects. Serum biological markers that are modulated by chronic corticosteroid use have not been identified. Myasthenia gravis is an autoimmune neuromuscular disorder caused by antibodies directed against proteins present at the post-synaptic surface … [Read more]
