Search results for "Myotonic Dystrophy"
showing 10 items of 54 documents
Gender as a Modifying Factor Influencing Myotonic Dystrophy Type 1 Phenotype Severity and Mortality: A Nationwide Multiple Databases Cross-Sectional …
2016
International audience; BACKGROUND: Myotonic Dystrophy type 1 (DM1) is one of the most heterogeneous hereditary disease in terms of age of onset, clinical manifestations, and severity, challenging both medical management and clinical trials. The CTG expansion size is the main factor determining the age of onset although no factor can finely predict phenotype and prognosis. Differences between males and females have not been specifically reported. Our aim is to study gender impact on DM1 phenotype and severity.METHODS: We first performed cross-sectional analysis of main multiorgan clinical parameters in 1409 adult DM1 patients (\textgreater18y) from the DM-Scope nationwide registry and obser…
Protective effects of mirtazapine in mice lacking the Mbnl2 gene in forebrain glutamatergic neurons: Relevance for myotonic dystrophy 1
2019
Myotonic dystrophy type 1 (DM1) is a multisystemic disorder characterized by muscle weakness and wasting and by important central nervous system-related symptoms including impairments in executive functions, spatial abilities and increased anxiety and depression. The Mbnl2 gene has been implicated in several phenotypes consistent with DM1 neuropathology. In this study, we developed a tissue-specific knockout mouse model lacking the Mbnl2 gene in forebrain glutamatergic neurons to examine its specific contribution to the neurobiological perturbations related to DM1. We found that these mice exhibit long-term cognitive deficits and a depressive-like state associated with neuronal loss, increa…
Noninvasive assessment of respiratory muscle strength and activity in Myotonic dystrophy
2017
Objective To evaluate sensitivity/specificity of the maximum relaxation rate (MRR) of inspiratory muscles, amplitude of electromyographic activity of the sternocleidomastoid (SCM), scalene (SCA), parasternal (2ndIS) and rectus abdominis (RA) muscles; lung function and respiratory muscle strength in subjects with Myotonic dystrophy type 1 (DM1) compared with healthy subjects. Design and methods Quasi-experimental observational study with control group. MRR of inspiratory muscles, lung function and amplitude of the electromyographic activity of SCM, SCA, 2ndIS and RA muscles during maximum inspiratory pressure (PImax), maximum expiratory pressure (PEmax) and sniff nasal inspiratory pressure (…
"I Know that You Know that I Know": Neural Substrates Associated with Social Cognition Deficits in DM1 Patients.
2016
Myotonic dystrophy type-1 (DM1) is a genetic multi-systemic disorder involving several organs including the brain. Despite the heterogeneity of this condition, some patients with non-congenital DM1 can present with minimal cognitive impairment on formal testing but with severe difficulties in daily-living activities including social interactions. One explanation for this paradoxical mismatch can be found in patients' dysfunctional social cognition, which can be assessed in the framework of the Theory of Mind (ToM). We hypothesize here that specific disease driven abnormalities in DM1 brains may result in ToM impairments. We recruited 20 DM1 patients who underwent the "Reading the Mind in th…
Expanded CTG repeats trigger miRNA alterations in Drosophila that are conserved in myotonic dystrophy type 1 patients
2013
Myotonic dystrophy type 1 (DM1) is caused by the expansion of CTG repeats in the 3' untranslated region of the DMPK gene. Several missplicing events and transcriptional alterations have been described in DM1 patients. A large number of these defects have been reproduced in animal models expressing CTG repeats alone. Recent studies have also reported miRNA dysregulation in DM1 patients. In this work, a Drosophila model was used to investigate miRNA transcriptome alterations in the muscle, specifically triggered by CTG expansions. Twenty miRNAs were differentially expressed in CTG-expressing flies. Of these, 19 were down-regulated, whereas 1 was up-regulated. This trend was confirmed for thos…
Retinopathia Pigmentosa Plus - the Value of Ultra-Structural Examination of the Human Retina
1993
Retinopathia pigmentosa is more widely, but somewhat incorrectly known as Retinitis pigmentosa (RP). Its course as a primary exclusively retinal disease follows autosomal-dominant, autosomal-recessive, or X-linked recessive modes of inheritance, or it may be sporadic. However, a progressive retinopathy, also called tapeto-retinal degeneration, may also be associated with numerous disorders: retinopathia pigmentosa plus (RPP). Among these RPP are those which form part of certain syndromes, e.g. Laurence-Moon-Bardet-Biedl syndrome, the Hallgren syndrome, the Marinesco-Sjogren syndrome, to name a few. Other RPP are associated with disorders of different organs, the skin, e.g. Werner disease, t…
Generación y caracterización de modelos en Drosophila de disfunción cardiaca en distrofia miotónica
2018
La tesis titulada "Generación y caracterización de los modelos de Drosophila de la disfunción cardíaca en la distrofia miotónica" se realiza mediante la combinación de tres artículos publicados. Después de la dificultad respiratoria, la disfunción cardíaca es la segunda causa más común de muerte asociada con la enfermedad neuromuscular distrofia miotónica (DM). A pesar de la participación central de la insuficiencia cardíaca en la DM, los estudios fisiopatológicos sobre los síntomas cardíacos han sido relativamente escasos porque pocos modelos murinos reproducen fielmente la enfermedad cardíaca. En consecuencia, solo un pequeño número de compuestos candidatos se han evaluado en este fenotip…
Development of aDrosophila melanogasterspliceosensor system forin vivohigh-throughput screening in myotonic dystrophy type 1
2014
AbstractAlternative splicing of pre-mRNAs is an important mechanism that regulates cellular function in higher eukaryotes. A growing number of human genetic diseases involve splicing defects that are directly connected to their pathology. In myotonic dystrophy type 1 (DM1), several clinical manifestations have been proposed to be the consequence of tissue-specific missplicing of numerous genes. These events are triggered by an RNA gain-of-function and resultant deregulation of specific RNA-binding factors, such as the nuclear sequestration of muscleblind-like family factors (MBNL1-MBNL3). Thus, the identification of chemical modulators of splicing events could lead to the development of the…
Neurophysiological and radiological findings in myotonic dystrophy patients
1999
Somatosensory evoked potentials (SEPs) and brainstem auditory evoked potentials (BAEPs) were recorded in 10 patients with myotonic dystrophy and in 20 sex and age-matched healthy controls. In all patients a brain MRI examination was also performed. In our results, the significantly longer absolute peak latencies of the SEPs and the abnormal increasing of the later components of the BAEPs suggest an involvement of the afferent sensory and central auditory pathways. Brain MRI showed white matter hyperintense lesions (WMHL) in eight patients (80%). No correlations were found between individual abnormal electrophysiological parameters or severity of WMHL and age, age at onset, disease duration …
Design of novel small molecule base-pair recognizers of toxic CUG RNA transcripts characteristics of DM1.
2020
Graphical abstract