Congenital myopathies
RSS feedThe manifestations of type 6 nemalin myopathy are modest but have a major impact on patients
A Dutch team has studied 24 patients with nemalin myopathy type 6, linked to mutations in KBTBD13 and the most prevalent in the Netherlands. Since childhood, patients have mainly suffered from muscle weakness, slowness of movement, muscle stiffness, difficulty running, fatigue and myalgia. Falls were reported by 71% of patients; over a prospective three-month period, … [Read more]
Cochrane meta-analysis in preparation on therapies for RYR1-related myopathies
An international consortium of clinicians led by a South African neuropaediatrician has presented a protocol designed to analyse the impact of different therapeutic interventions in muscle-expressing diseases associated with abnormalities of the RYR1 gene: the study will be based on the Cochrane methodology for meta-analysis of the literature on the subject, 7 experts have been … [Read more]
Targeted inhibition of ORAI1 reduces tubular aggregates in mice
Tubular aggregate myopathy may be due to overactivation of Store Operated Ca2+ Entry (SOCE) as a result of a gain-of-function variant in the STIM1 or ORAI1 genes. ORAI1 is a T-tubule membrane calcium channel that is activated by STIM1, a sarcoplasmic reticulum membrane protein that senses depletion of intracellular calcium stores. KO mice for ORAI1 … [Read more]
Mavacamten for 4 weeks does not improve the condition of mice models of nebulin-related nemalin myopathy
In muscle fibers from individuals with nebulin-related nemaline myopathy (NEB-NM) and in NEB-NM mouse models, the proportion of myosin in the disordered relaxed state and ATP consumption are abnormally increased, accompanied by a reshuffling of the energy proteome of these cells. Mavacamten, which reduces the amount of myosin in the disordered relaxed state in hypertrophic … [Read more]
Loss of function of JPH1, which encodes junctophilin, causes congenital myopathy
Four individuals from unrelated consanguineous families, two of European origin, one of Khmer origin and one of Middle Eastern origin all presented with congenital myopathy with: neonatal hypotonia, difficulty sucking, cleft palate, club feet ; generalized weakness predominantly in the lower limbs; myopathic facies, bilateral ptosis, ophthalmoplegia and fatigability; muscle biopsy revealed a predominance of … [Read more]
Overview of the main myopathies that can begin in the over-50s
A French review has set out to provide an overview of the most emblematic late-onset myopathies (LOMs), those which may appear after the age of 50, and to identify the pitfalls to be avoided and the important steps in the diagnostic approach to these pathologies. Based on an assessment of the literature and medical data … [Read more]
The SH3 domain interactome of amphiphysin 2 in centronuclear myopathies
While amphiphysin 2 uses its BAR domain to anchor to cell membranes and cause them to bend, it also has an SH3 domain at the other end that enables it to interact with other proteins, in particular dynamin 2, cavin 4 or another amphiphysin 2 molecule. Using a new approach to studying the interactome, the … [Read more]
The MYOCAPTURE project improves molecular understanding of congenital myopathies
Between 2009 and 2018, whole exome sequencing of 310 families affected by congenital myopathy as part of the MYOCAPTURE project, supported by the AFM-Téléthon, identified 14 new genes: four linked to other neuromuscular diseases or cardiomyopathy (ASCC1, HSPB8, CACNA1S, MYPN), ten never implicated in a genetic neuromuscular disease (ACTN2, CASQ1, GGPS1, MAP3K20/ZAK, ORAI1, MYO18B, PYROXD1, … [Read more]
Congenital myopathy linked to the STAC3 gene is a frequent cause of early hypotonia in South Africa
South African researchers report the clinical and biological data from a cohort of 127 young children with congenital hypotonia: they had been previously excluded for SMA and Prader-Willi syndrome, the homozygous variant identified in STAC3 by high-throughput DNA sequencing in 31 children is the same as that found in patients from Africa, additional haplotyping studies … [Read more]
Dominant CACNA1S mutations: pure myopathic forms are possible
Dominant mutations of the CACNA1S gene most often cause hypokalemic periodic paralysis or malignant hyperthermia. The team at the Brussels Neuromuscular Reference Centre reports the case of a 65-year-old man with progressive proximal muscle weakness that began at the age of 35, without any transient paralysis: his mother, who had been in a wheelchair since … [Read more]
