Blog Archives

In this study, the authors aimed to assess the frequency, location, severity, duration, and fluctuation over time of muscle cramps in Charcot-Marie-Tooth Disease (CMT). Inherited Neuropathies Consortium Contact Registry participants recorded the occurrence and characteristics of muscle cramps using an 11-question survey administered 3 times over 8 weeks. A  total of 110 adult patients with … [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]

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]

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]

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]

Most mutations that truncate the reading frame of the DMD gene cause loss of dystrophin expression and lead to Duchenne muscular dystrophy. However, amelioration of disease severity has been shown to result from alternative translation initiation beginning in DMD exon 6 that leads to expression of a highly functional N-truncated dystrophin. Here, the authors demonstrate … [Read more]

Isis Pharmaceuticals has initiated a pivotal Phase III study evaluating ISIS-SMNRx in infants with spinal muscular atrophy (SMA), the most common genetic cause of infant mortality. The Phase III study entitled ENDEAR, is the first of several planned studies in a broad and comprehensive late-stage clinical development program for ISIS-SMNRx.  ENDEAR is a randomized, double-blind, … [Read more]

There are no validated criteria for the diagnosis of sensory neuronopathy (SNN) yet. In a preliminary monocenter study, a set of criteria relying on clinical and electrophysiological data showed good sensitivity and specificity for a diagnosis of probable SNN. The aim of this study was to test these criteria in a French multicenter study. A … [Read more]

Centronuclear myopathies (CNMs) are characterized by muscle weakness and increased numbers of central nuclei within myofibers. X-linked myotubular myopathy, the most common severe form of CNM, is caused by mutations in MTM1, encoding myotubularin (MTM1), a lipid phosphatase. To increase understanding of MTM1 function, the authors of this study conducted a yeast two-hybrid screen to … [Read more]

Pompe disease is a rare, autosomal recessive disorder characterized by deficiency of lysosomal acid alpha-glucosidase and accumulation of lysosomal glycogen in many tissues. The variable clinical manifestations, broad phenotypic spectrum, and overlap of signs and symptoms with other neuromuscular diseases make diagnosis challenging. In the past, the diagnosis of Pompe disease was based on enzyme … [Read more]