Myology research highlights
RSS feedCongenital muscular dystrophy and generalized epilepsy caused by GMPPB mutations
The alpha-dystroglycanopathies are genetically heterogeneous muscular dystrophies that result from hypoglycosylation of alpha-dystroglycan (α-DG). Alpha-dystroglycan is an essential link between the extracellular matrix and the muscle fiber sarcolemma, and proper glycosylation is critical for its ability to bind to ligands in the extracellular matrix. Here, the authors sought to identify the genetic basis of alpha-dystroglycanopathy … [Read more]
First meta-analysis of worldwide prevalence estimates for muscular dystrophies
The muscular dystrophies are a broad group of hereditary muscle diseases with variable severity. Population-based prevalence estimates have been reported but pooled estimates are not available. Here, the authors performed a systematic review of worldwide population-based studies reporting muscular dystrophies prevalence and/or incidence using MEDLINE and EMBASE databases. The search strategy included key terms related … [Read more]
A new penetrant and specific test to diagnose Giant Axonal Neuropathy
The BTB-KELCH protein Gigaxonin plays key roles in sustaining neuron survival and cytoskeleton architecture. Indeed, recessive mutations in the Gigaxonin-encoding gene cause Giant Axonal Neuropathy (GAN), a severe neurodegenerative disorder characterized by a wide disorganization of the Intermediate Filament network. Growing evidence suggests that GAN is a continuum with the peripheral neuropathy Charcot-Marie-Tooth diseases type … [Read more]
Peripheral Myelin Protein 22 gene duplication with atypical presentations: A new example of the wide spectrum of Charcot-Marie-Tooth 1A disease
Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are both autosomal-dominant disorders linked to peripheral myelin anomalies. CMT1A is associated with a Peripheral Myelin Protein 22 (PMP22) duplication, whereas HNPP is due to a PMP22 deletion on chromosome 17. In spite of this crucial difference, the authors report three observations … [Read more]
Whole-genome sequencing and the clinician: a tale of two cities
Clinicians are faced with unprecedented opportunities to identify the genetic aetiologies of hitherto molecularly uncharacterised conditions via the use of high-throughput sequencing. Access to genomic technology and resultant data is no longer limited to clinicians, geneticists and bioinformaticians, however; ongoing commercialisation gives patients themselves ever greater access to sequencing services. The authors report an increasingly … [Read more]
A novel mutation in the MTTM gene causes mitochondrial myopathy with dystrophic features
A 61-year-old woman with a five-year history of progressive muscle weakness and atrophy had a muscle biopsy characterized by a combination of dystrophic features (necrotic fibers and endomysial fibrosis) and mitochondrial alterations [ragged-red cytochrome c oxidase (COX)-negative fibers]. Sequencing of the whole mtDNA, assessment of the mutation load in muscle and in accessible non-muscle tissues, … [Read more]
Nemaline myopathy caused byTNNT1 mutations in a Dutch pedigree
Nemaline myopathy (NM) is a genetically heterogeneous disorder characterized by early onset muscular weakness and sarcoplasmatic or intranuclear inclusions of rod-shaped Z-disk material in muscle fibers. Thus far, mutations in seven genes have been identified as the cause of NM. Only one singleTNNT1 nonsense mutation has been previously described that causes autosomal recessive NM in … [Read more]
Genotype-phenotype correlations of novel and previously described mutations in TPM2 and TPM3
Mutations affecting skeletal muscle isoforms of the tropomyosin genes may cause nemaline myopathy (NM), cap myopathy, core-rod myopathy, congenital fibre-type disproportion, distal arthrogryposes and Escobar syndrome. This study correlates the clinical picture of these diseases with novel (16) and previously reported (31) mutations of the TPM2 and TPM3 genes. Altogether 93 families are included: 53 … [Read more]
Plasma microRNAs as biomarkers for DM1
Myotonic dystrophy type 1 (DM1) lacks non-invasive and easy to measure biomarkers, still largely relying on semi-quantitative tests for diagnostic and prognostic purposes. Muscle biopsies provide valuable data, but their use is limited by their invasiveness. microRNA (miRNAs) are small non-coding RNAs regulating gene expression that are also present in biological fluids and may serve … [Read more]
Targeting toxic RNAs to reverse myotonia and other symptoms of DM1
A working hypothesis for the pathogenesis of myotonic dystrophy type 1 (DM1) involves the aberrant sequestration of an alternative splicing regulator, MBNL1, by expanded CUG repeats, r(CUG)exp. It has been suggested that a reversal of the myotonia and potentially other symptoms of the DM1 disease can be achieved by inhibiting the toxic MBNL1-r(CUG)exp interaction. Using … [Read more]
