Myology research highlights

Scoliosis in patients with Duchenne muscular dystrophy (DMD) is usually progressive and is treated with surgery. However, it is unclear whether the existing evidence is sufficiently scientifically rigorous to support a recommendation for spinal surgery for most patients with DMD and scoliosis. In this updated review, the authors aimed to determine the effectiveness and safety … [Read more]

Becker muscular dystrophy (BMD) is caused by in-frame mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the sarcolemma. Among these is neuronal nitric oxide synthase (nNOSμ), which requires specific spectrin-like repeats (SR16/17) in dystrophin’s rod domain and the adaptor protein α-syntrophin for sarcolemmal targeting. When healthy skeletal … [Read more]

This study aimed to translate whole-exome sequencing (WES) to clinical practice for the genetic diagnosis of a large cohort of patients with limb-girdle muscular dystrophy (LGMD) for whom protein-based analyses and targeted Sanger sequencing failed to identify the genetic cause of their disorder. WES was carried out on 60 families with LGMDs (100 exomes), who … [Read more]

The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare autoimmune diseases characterised by muscle weakness and extramuscular manifestations such as skin rashes and interstitial lung disease. Herein, the authors genotyped 2566 IIM cases of Caucasian descent using the Immunochip; a custom array covering 186 established autoimmune susceptibility loci. The cohort was predominantly comprised … [Read more]

A recombinant serotype 9 adeno-associated virus (rAAV9) vector carrying a transgene that expresses codon-optimized human acid alpha-glucosidase (hGAA, or GAA) driven by a human desmin (DES) promoter (i.e., rAAV9-DES-hGAA) is being developed as a treatment for both early- and late-onset Pompe disease. In Pompe disease, patients lack sufficient lysosomal alpha-glucosidase leading to glycogen accumulation. In … [Read more]

Exon duplication mutations account for up to 11% of all cases of Duchenne muscular dystrophy (DMD), and a duplication of exon 2 is the most common duplication in patients. For use as a platform for testing of duplication-specific therapies, the authors of the present study developed a mouse model that carries a Dmd exon 2 … [Read more]

Limb-girdle muscular dystrophy type 1D (LGMD1D) is caused by dominantly inherited missense mutations in DNAJB6, an Hsp40 co-chaperone. LGMD1D muscle has rimmed vacuoles and inclusion bodies containing DNAJB6, Z-disc proteins and TDP-43. DNAJB6 is expressed as two isoforms; DNAJB6a and DNAJB6b. Both isoforms contain LGMD1D mutant residues and are expressed in human muscle. To identify … [Read more]

In this study, the authors evaluated, by skin biopsy, dermal nerve fibers in 31 patients with 3 common Charcot-Marie-Tooth (CMT) genotypes and rarer forms of CMT caused by mutations in RAB7 and GDAP1 genes. Axonal loss examinations revealed that the density of both Meissner corpuscles and intrapapillary myelinated endings was reduced in skin samples from … [Read more]

Merosin-deficient congenital muscular dystrophy type-1A (MDC1A) is characterised by progressive muscular dystrophy and dysmyelinating neuropathy caused by mutations of the α2 chain of laminin-211, the predominant laminin isoform of muscles and nerves. MDC1A has no available treatment so far, although preclinical studies showed amelioration of the disease by the overexpression of miniagrin (MAG). MAG reconnects … [Read more]

Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy in adults. DM1 is caused by an expanded CTG repeat in the 3′- untranslated region of DMPK, the gene encoding Dystrophia Myotonica-Protein Kinase. ASOs containing constrained ethyl-modified (cEt) residues exhibit significantly increased RNA binding affinity and in vivo potency relative to those … [Read more]