Myology research highlights

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]

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]

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]

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]

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]

In this study, the authors characterized the phenotype of patients with distal myopathy with vocal cord and pharyngeal weakness (VCPDM) due to the p.S85C mutation in the Matrin 3 gene (MATR3, MIM 164015). Recently it has been suggested that patients with this mutation may suffer from familial amyotrophic lateral sclerosis. Sixteen patients from six families … [Read more]

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 (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]

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]

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]