Search results for " Limb-Girdle"

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Inhibition of autophagy rescues muscle atrophy in a LGMDD2 Drosophila model

2021

Limb-girdle muscular dystrophy D2 (LGMDD2) is an ultrarare autosomal dominant myopathy caused by mutation of the normal stop codon of the TNPO3 nuclear importin. The mutant protein carries a 15 amino acid C-terminal extension associated with pathogenicity. Here we report the first animal model of the disease by expressing the human mutant TNPO3 gene in Drosophila musculature or motor neurons and concomitantly silencing the endogenous expression of the fly protein ortholog. A similar genotype expressing wildtype TNPO3 served as a control. Phenotypes characterization revealed that mutant TNPO3 expression targeted at muscles or motor neurons caused LGMDD2-like phenotypes such as muscle degener…

MaleMutantBiochemistryAnimals Genetically ModifiedMutant proteinAutophagyGeneticsmedicineAnimalsHumansGene silencingMuscular dystrophyMyopathyMolecular BiologyMotor NeuronsbiologyMusclesAutophagyChloroquinebeta Karyopherinsmedicine.diseasebiology.organism_classificationMuscle atrophyCell biologySurvival RateDisease Models AnimalMuscular AtrophyDrosophila melanogasterPhenotypeMuscular Dystrophies Limb-GirdleInsect HormonesFemalemedicine.symptomDrosophila melanogasterLocomotionBiotechnologyThe FASEB Journal
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Eight new mutations and the expanding phenotype variability in muscular dystrophy caused by ANO5.

2012

Objective: Description of 8 new ANO5 mutations and significant expansion of the clinical phenotype spectrum associated with previously known and unknown mutations to improve diagnostic accuracy. Methods: DNA samples of 101 patients in 95 kindreds at our quaternary referral center in Finland, who had undetermined limb-girdle muscular dystrophy (LGMD), calf distal myopathy, or creatine kinase (CK) elevations of more than 2,000 IU/L, were selected for ANO5 genetic evaluation, and the clinical findings of patients with mutations were retrospectively analyzed. Results: A total of 25 patients with muscular dystrophy caused by 11 different recessive mutations in the ANO5 gene were identified. The …

myalgiaMalePathologymedicine.disease_causeCohort Studies0302 clinical medicineMedicineMuscular dystrophyAge of OnsetCreatine KinaseFinland0303 health sciencesMutationMuscle WeaknessbiologyMiddle AgedPhenotypeMagnetic Resonance Imaging3. Good healthPhenotypeFemalemedicine.symptomAdultmedicine.medical_specialtyWeaknessGenotypeBlotting WesternAnoctaminsGenes RecessiveAsymptomatic03 medical and health sciencesChloride ChannelsHumansGenetic TestingMyopathyMuscle Skeletal030304 developmental biologyAgedbusiness.industryGenetic VariationReproducibility of ResultsDNAmedicine.diseaseMuscular Dystrophies Limb-GirdleMutationbiology.proteinCreatine kinaseNeurology (clinical)business030217 neurology & neurosurgeryNeurology
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