Myology research highlights

The pathogenic mechanisms for idiopathic myositis (or inflammatory myopathies) are becoming ever clearer. In particular, they involve interferons (IFNs), whose role has been demonstrated by the transcriptome analysis of tissues or cells taken from patients with myositis, which shows an increase in the expression of IFN stimulated genes (ISGs): there is talk of an “interferon … [Read more]

Myotonic dystrophy type 1 (DM1) is a life-threatening and chronically debilitating neuromuscular disease caused by the expansion of a CTG trinucleotide repeat in the 3′ UTR of the DMPK gene. The mutant RNA forms insoluble structures capable of sequestering RNA binding proteins of the Muscleblind-like (MBNL) family, which ultimately leads to phenotypes. In this work, … [Read more]

The prevalence of arterial hypertension in mitochondrial diseases remains unknown. Between January 2000 and May 2014, a team of French clinicians, including clinicians from the Institut of Myology, retrospectively included patients with genetically proven mitochondrial diseases. We recorded clinical, genetic and cardiac exploration data, including the measure of arterial pressure. Among the 260 patients included … [Read more]

Translarna (ataluren) is the first drug to have obtained a conditional marketing authorization in Europe, in Duchenne muscular dystrophy: On July 31, 2014, the conditional marketing authorization was issued by the EMA only for children with DMD aged 5 years and over, walking and having a nonsense mutation in the DMD gene. On May 31, … [Read more]

The coordinated expression of myogenic regulatory factors, including MyoD and myogenin, orchestrates the steps of skeletal muscle development, from myoblast proliferation and cell-cycle exit, to myoblast fusion and myotubes maturation. Yet, it remains unclear how key transcription factors and epigenetic enzymes cooperate to guide myogenic differentiation. Proteins of the SMYD (SET and MYND domain-containing) methyltransferase … [Read more]

Charcot-Marie-Tooth 1A (CMT1A) is the most common inherited neuropathy without a known therapy, which is caused by a 1.4 Mb duplication on human chromosome 17, which includes the gene encoding the peripheral myelin protein of 22 kDa (PMP22). Overexpressed PMP22 protein from its gene duplication is thought to cause demyelination and subsequently axonal degeneration in … [Read more]

Loss of ambulation in Duchenne muscular dystrophy presages scoliosis, respiratory failure, and death. Strategies to maintain ankle range of motion are employed, but little evidence exists to support these approaches and limited information is available concerning current practice. In this study the researchers assessed baseline bracing data from 187 boys participating in a multicenter, international … [Read more]

The Popeye domain containing 3 (POPDC3) gene encodes a membrane protein involved in cyclic adenosine monophosphate (cAMP) signaling. Besides gastric cancer, no disease association has been described. The authors describe a new muscular dystrophy associated with this gene. They screened 1,500 patients with unclassified limb girdle weakness or hyperCKemia for pathogenic POPDC3 variants. Five patients … [Read more]

Next-generation sequencing (NGS) was applied in molecularly undiagnosed asymptomatic or paucisymptomatic hyperCKemia to investigate whether this technique might allow detection of the genetic basis of the condition. Sixty-six patients with undiagnosed asymptomatic or paucisymptomatic hyperCKemia, referred to tertiary neuromuscular centers over an approximately 2-year period, were analyzed using a customized, targeted sequencing panel able to … [Read more]

Spinal Muscular Atrophy (SMA), an autosomal recessive neurodegenerative disease characterized by the loss of spinal-cord motor-neurons, is caused by mutations on Survival-of-Motor Neuron (SMN)-1 gene. The expression of SMN2, a SMN1 gene copy, partially compensates for SMN1 disruption due to exon-7 excision in 90% of transcripts subsequently explaining the strong clinical heterogeneity. Several alterations in … [Read more]