Blog Archives
New type of histological abnormalities in congenital nemaline myopathies
French clinicians report, in five patients with congenital rod myopathy (also called nemaline), histological lesions in the form of dense protein masses: none of the patients were related, in three of them pathological variants of the NEB gene encoding nebulin were identified, in another, the TPM2 gene encoding tropomyosin-2 was involved, the clinical phenotype was … [Read more]
Phenylbutyrate restores dysferlin localization and membrane repair in cellular and animal models of dysferlinopathies
Missense mutations account for 30 to 40% of abnormalities responsible for dysferlinopathy. They generate abnormal, misfolded and unstable dysferlins, which can result in an absence of dysferlin at the plasma membrane in immunocytochemistry. An international team has developed a technique based on flow cytometry to measure the amount of dysferlin localized to the cell membrane … [Read more]
Calpain 1 gene involved in spinal muscular atrophy type 4 unrelated to SMN1
Whole genome sequencing of a brother and sister with an adult-onset form of SMA without mutation in the SMN1 gene revealed a compound heterozygous mutation in the CAPN1 gene. It encodes calpain 1, a ubiquitous calcium-dependent protease. The first signs (painless muscle weakness, tendency to fall, cramps in the upper and lower limbs after exercise) … [Read more]
Splicing efficiency of minor introns in a mouse model of SMA
Spinal muscular atrophy (SMA) is a devastating neurodegenerative disease caused by mutations in the SMN1 gene resulting in a decreased expression of the ubiquitous SMN protein. Given the crucial role of this SMN protein in the biogenesis of spliceosomal snRNPs (small nuclear ribonucleoproteins), the deficiency of this protein is correlated with numerous splicing alterations in … [Read more]
A natural microRNA spiked with small molecules to knock down DUX4 in FSHD
Facioscapulohumeral muscular dystrophy (FSHD or FSH) is characterized by an aberrant expression of the DUX4 gene. To prevent it, in a gene silencing approach, a therapeutic avenue consists in specifically binding the messenger RNA of DUX4 to synthetic RNAs of the complementary siRNA or miRNA type. In the United States, a team of gene therapy … [Read more]
Myasthenia gravis: launch of the MYaEX study
The Institute of Myology and AFM-Telethon have launched MYaEX, a large national survey regarding persons with myasthenia gravis, congenital myasthenic syndrome or Lambert Eaton myasthenic syndrome. The main objective of this study is to help to understand what determines the practice of physical exercise in these pathologies of the neuromuscular junction, and to identify the factors … [Read more]
Searching for protective factors against cancer risk in dermatomyositis
American researchers were interested in patients with dermatomyositis who did not develop cancers in addition to their muscle disease. Their immunological profile has been studied in the hope of identifying cancer risk factors other than the already known one of anti-TIF1-g autoantibody positivity: 10 new autoantibodies have been identified in two distinct cohorts of patients … [Read more]
Systemic injection of an optimized antisense oligonucleotide into an FSH mouse model appears to be effective
Facioscapulohumeral dystrophy (FSH) is one of the most common myopathies. There are two forms, FSH1 and FSH2. In both cases, the DUX4 gene is abnormally expressed in the muscles. In an effort to inhibit DUX4, Canadian researchers have optimized antisense oligonucleotides by coupling them to a peptide that favors their penetration into muscle cells. This optimized … [Read more]
A catalog of sodium channel variants to guide in the diagnosis of certain myotonic syndromes
An international consortium of researchers has catagorized, based on literature data, the biophysical and genetic characteristics of 437 sodium channel variants known to date (including the sodium channel encoded by the SCN4A gene): 79 of them were related to a muscular phenotype (corresponding to a myotonic syndrome in most cases), 141 variants corresponded to epileptic … [Read more]
An innovative test for the genotyping of difficult cases of DMD and a better pathophysiological approach
Italian researchers have developed, in conjunction with the Perkin-Elmer laboratory, a test based on RNA sequencing (RNA-seq) to detect and interpret the pathogenic nature of certain variants of the DMD gene encoding the dystrophin on simple urine samples: the test analyzes DMD gene transcripts present in stem cells detectable in small amounts in urine; the … [Read more]
