RYR1 is the most commonly mutated gene associated with congenital myopathies, a group of early-onset neuromuscular conditions of variable severity. The functional effects of a number of dominant RYR1 mutations have been established; however, for recessive mutations, these effects may depend on multiple factors, such as the formation of a hypomorphic allele, or on whether they are homozygous or compound heterozygous. Here, we functionally characterize a new transgenic mouse model knocked-in for mutations identified in a severely affected child born preterm and presenting limited limb movement.
View Article and Find Full Text PDFSkeletal muscles are a highly structured tissue responsible for movement and metabolic regulation, which can be broadly subdivided into fast and slow twitch muscles with each type expressing common as well as specific sets of proteins. Congenital myopathies are a group of muscle diseases leading to a weak muscle phenotype caused by mutations in a number of genes including . Patients carrying recessive mutations usually present from birth and are generally more severely affected, showing preferential involvement of fast twitch muscles as well as extraocular and facial muscles.
View Article and Find Full Text PDFDrug repurposing can overcome both substantial costs and the lengthy process of new drug discovery and development in cancer treatment. Some Food and Drug Administration (FDA)-approved drugs have been found to have the potential to be repurposed as anti-cancer drugs. However, the progress is slow due to only a handful of strategies employed to identify drugs with repurposing potential.
View Article and Find Full Text PDFTo date there are no therapies for patients with congenital myopathies, muscle disorders causing poor quality of life of affected individuals. In approximately 30% of the cases, patients with congenital myopathies carry either dominant or recessive mutations in the ryanodine receptor 1 () gene; recessive mutations are accompanied by reduction of RyR1 expression and content in skeletal muscles and are associated with fiber hypotrophy and muscle weakness. Importantly, muscles of patients with recessive mutations exhibit increased content of class II histone deacetylases and of DNA genomic methylation.
View Article and Find Full Text PDFInt J Ment Health Addict
October 2021
Background: Risk perception about COVID-19 constitutes an important variable contributing to promotion of personal protection practices. The aims of this study were to exploring the factorial structure of the risk perception COVID-19 scale (RP-COVID19-S) in a sample of Cuban adults and to identify its relationship with variables such as gender and age.
Methods: A cross-sectional web-based survey design was conducted.
Mutations in the ryanodine receptor 1 () gene are associated with several human congenital myopathies, including the dominantly inherited central core disease and exercise-induced rhabdomyolysis, and the more severe recessive phenotypes, including multiminicore disease, centronuclear myopathy, and congenital fiber type disproportion. Within the latter group, those carrying a hypomorphic mutation in one allele and a missense mutation in the other are the most severely affected. Because of nonsense-mediated decay, most hypomorphic alleles are not expressed, resulting in homozygous expression of the missense mutation allele.
View Article and Find Full Text PDFMutations in the RYR1 gene are the most common cause of human congenital myopathies, and patients with recessive mutations are severely affected and often display ptosis and/or ophthalmoplegia. In order to gain insight into the mechanism leading to extraocular muscle (EOM) involvement, we investigated the biochemical, structural and physiological properties of eye muscles from mouse models we created knocked-in for Ryr1 mutations. Ex vivo force production in EOMs from compound heterozygous RyR1p.
View Article and Find Full Text PDFExplanatory models (EMs) for illness are highly relevant for patients, and they are also important for clinical diagnoses and treatment. EMs serve to capture patients' personal illness narratives and can help reveal how culture influences these narratives. While much research has aimed to understand EMs in the Western hemisphere, less research has been done on other cultures.
View Article and Find Full Text PDFRecessive ryanodine receptor 1 (RYR1) mutations cause congenital myopathies including multiminicore disease (MmD), congenital fiber-type disproportion and centronuclear myopathy. We created a mouse model knocked-in for the Q1970fsX16+A4329D RYR1 mutations, which are isogenic with those identified in a severely affected child with MmD. During the first 20 weeks after birth the body weight and the spontaneous running distance of the mutant mice were 20% and 50% lower compared to wild-type littermates.
View Article and Find Full Text PDFHere we characterized a mouse model knocked-in for a frameshift mutation in RYR1 exon 36 (p.Gln1970fsX16) that is isogenic to that identified in one parent of a severely affected patient with recessively inherited multiminicore disease. This individual carrying the RYR1 frameshifting mutation complained of mild muscle weakness and fatigability.
View Article and Find Full Text PDFSeveral theories describing the decision-making process in the intensive care unit (ICU) have been formulated. However, none of them appreciate the complexities of the process in an eclectic way by unifying several miscellaneous variables in 1 comprehensive theory. The purpose of this review is to highlight the key intricacies associated with the decision-making process in the ICU, to describe the theoretical frameworks with a special emphasis on gaps of knowledge, and to offer some avenues for improvement.
View Article and Find Full Text PDFSRP-35 is a short-chain dehydrogenase/reductase belonging to the DHRS7C dehydrogenase/ reductase family 7. Here we show that its over-expression in mouse skeletal muscles induces enhanced muscle performance in vivo, which is not related to alterations in excitation-contraction coupling but rather linked to enhanced glucose metabolism. Over-expression of SRP-35 causes increased phosphorylation of Akt, triggering plasmalemmal targeting of GLUT4 and higher glucose uptake into muscles.
View Article and Find Full Text PDF