Myology research highlights

This study evaluated primary and secondary clinical outcome measures in Charcot-Marie-Tooth disease type 1A (CMT1A) with regard to their contribution towards discrimination of disease severity. The nine components of the composite Charcot-Marie-Tooth disease Neuropathy Score and six additional secondary clinical outcome measures were assessed in 479 adult patients with genetically proven CMT1A and 126 healthy … [Read more]

The goal of this study was to describe a novel mutation in TRK-fused gene (TFG) as a new cause of dominant axonal Charcot-Marie-Tooth disease (CMT) identified by exome sequencing and further characterized by in vitro functional studies. Exome sequencing and linkage analysis were used to investigate a large Taiwanese family with a dominantly inherited adult-onset … [Read more]

Nondystrophic myotonias are characterized by muscle stiffness triggered by voluntary movement. They are caused by mutations in either the CLCN1 gene in myotonia congenita or in the SCN4A gene in paramyotonia congenita and sodium channel myotonias. Clinical and electrophysiological phenotypes of these disorders have been well described. No concomitant mutations in both genes have been … [Read more]

Spinal muscular atrophy (SMA) is a genetic disease caused by mutation or deletion of the survival of motor neuron 1 (SMN1) gene. A paralogous gene in humans, SMN2, produces low, insufficient levels of functional SMN protein due to alternative splicing that truncates the transcript. The decreased levels of SMN protein lead to progressive neuromuscular degeneration … [Read more]

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]

In facioscapulohumeral dystrophy (FSHD), hypomethylation is moderate and heterogeneous in patients. To date, a correlation between hypomethylation and disease presence or severity has not been demonstrated. Here, the authors investigated the link between DNA hypomethylation and clinical penetrance in 95 FSHD cases (37 FSHD1, 29 asymptomatic individuals carrying a shortened D4Z4 array, 9 patients with … [Read more]

The investigational oral drug ataluren, in development to treat Duchenne muscular dystrophy (DMD) resulting from a specific type of genetic mutation, has received conditional approval in the European Union (EU). This designation allows patients to gain access to an experimental drug before it is fully approved. Ataluren, originally known as PTC124 and now bearing the … [Read more]

Dystrophinopathy is a rare, severe muscle disorder, and nonsense mutations are found in 13% of cases. Ataluren was developed to enable ribosomal readthrough of premature stop codons in nonsense mutation (nm) genetic disorders. In this randomized, double-blind, placebo-controlled study males ≥5 years with nm-dystrophinopathy received study drug orally 3 times daily, ataluren 10, 10, 20 … [Read more]

Duchenne and Becker muscular dystrophy (DBMD) are allelic disorders caused by mutations in dystrophin. Patients with DBMB lack neuronal nitric oxide synthase (nNOS), which mediates physiological sympatholysis, thus ensuring adequate blood supply to working muscle. In mice lacking dystrophin, restoration of nNOS effects by a phosphodiesterase 5 (PDE5) inhibitor (sildenafil), improves skeletal and cardiac muscle … [Read more]

No treatment is available for patients affected by the recessively inherited, progressive muscular dystrophies caused by a deficiency in the muscle membrane repair protein dysferlin. A marked reduction in dysferlin in patients harboring missense mutations in at least one of the two pathogenic DYSF alleles encoding dysferlin implies that dysferlin is degraded by the cell’s … [Read more]