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Zeitschriftenartikel zum Thema "Myotonic Dystrophy type 1 (DM1)"
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García-Puga, Mikel, Ander Saenz-Antoñanzas, Ander Matheu und Adolfo López de Munain. „Targeting Myotonic Dystrophy Type 1 with Metformin“. International Journal of Molecular Sciences 23, Nr. 5 (07.03.2022): 2901. http://dx.doi.org/10.3390/ijms23052901.
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Myotonic dystrophy type 1 (DM1) is a multisystemic disorder of genetic origin. Progressive muscular weakness, atrophy and myotonia are its most prominent neuromuscular features, while additional clinical manifestations in multiple organs are also common. Overall, DM1 features resemble accelerated aging. There is currently no cure or specific treatment for myotonic dystrophy patients. However, in recent years a great effort has been made to identify potential new therapeutic strategies for DM1 patients. Metformin is a biguanide antidiabetic drug, with potential to delay aging at cellular and organismal levels. In DM1, different studies revealed that metformin rescues multiple phenotypes of the disease. This review provides an overview of recent findings describing metformin as a novel therapy to combat DM1 and their link with aging.
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Soltanzadeh, Payam. „Myotonic Dystrophies: A Genetic Overview“. Genes 13, Nr. 2 (17.02.2022): 367. http://dx.doi.org/10.3390/genes13020367.
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Myotonic dystrophies (DM) are the most common muscular dystrophies in adults, which can affect other non-skeletal muscle organs such as the heart, brain and gastrointestinal system. There are two genetically distinct types of myotonic dystrophy: myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2), both dominantly inherited with significant overlap in clinical manifestations. DM1 results from CTG repeat expansions in the 3′-untranslated region (3′UTR) of the DMPK (dystrophia myotonica protein kinase) gene on chromosome 19, while DM2 is caused by CCTG repeat expansions in intron 1 of the CNBP (cellular nucleic acid-binding protein) gene on chromosome 3. Recent advances in genetics and molecular biology, especially in the field of RNA biology, have allowed better understanding of the potential pathomechanisms involved in DM. In this review article, core clinical features and genetics of DM are presented followed by a discussion on the current postulated pathomechanisms and therapeutic approaches used in DM, including the ones currently in human clinical trial phase.
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Romigi, A., M. Albanese, C. Liguori, F. Placidi, M. G. Marciani und R. Massa. „Sleep-Wake Cycle and Daytime Sleepiness in the Myotonic Dystrophies“. Journal of Neurodegenerative Diseases 2013 (04.11.2013): 1–13. http://dx.doi.org/10.1155/2013/692026.
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Myotonic dystrophy is the most common type of muscular dystrophy in adults and is characterized by progressive myopathy, myotonia, and multiorgan involvement. Two genetically distinct entities have been identified, myotonic dystrophy type 1 (DM1 or Steinert’s Disease) and myotonic dystrophy type 2 (DM2). Myotonic dystrophies are strongly associated with sleep dysfunction. Sleep disturbances in DM1 are common and include sleep-disordered breathing (SDB), periodic limb movements (PLMS), central hypersomnia, and REM sleep dysregulation (high REM density and narcoleptic-like phenotype). Interestingly, drowsiness in DM1 seems to be due to a central dysfunction of sleep-wake regulation more than SDB. To date, little is known regarding the occurrence of sleep disorders in DM2. SDB (obstructive and central apnoea), REM sleep without atonia, and restless legs syndrome have been described. Further polysomnographic, controlled studies are strongly needed, particularly in DM2, in order to clarify the role of sleep disorders in the myotonic dystrophies.
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Kitsis, Elizabeth A., Fabreena Napier, Viral Juthani und Howard L. Geyer. „Association of Sjögren’s syndrome with myotonic dystrophy type 1“. BMJ Case Reports 12, Nr. 8 (August 2019): e229611. http://dx.doi.org/10.1136/bcr-2019-229611.
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A 47-year-old woman presented with sicca symptoms, polyarthralgias, polymyalgias and dysphagia. She was found to have positive antinuclear, anti-SSA-Ro and anti-SSB-La antibodies. Slit lamp exam confirmed the presence of keratoconjunctivitis sicca, and the patient was diagnosed with Sjögren’s syndrome. Three years later, she was referred for evaluation of gait instability associated with recent falls. On physical examination, the patient was found to have bilateral ptosis, percussion myotonia, distal upper and lower extremity weakness, and a steppage gait. Electromyography demonstrated electrical myotonia. Genetic testing revealed expanded CTG repeats (733 and 533) in the myotonic dystrophy type 1 (DM1) protein kinase gene, confirming the diagnosis of DM1. Dysphagia, pain and eye discomfort may occur in both Sjögren’s syndrome and DM1, and in this case, may have delayed the diagnosis of muscular dystrophy.
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Souidi, Anissa, Monika Zmojdzian und Krzysztof Jagla. „Dissecting Pathogenetic Mechanisms and Therapeutic Strategies in Drosophila Models of Myotonic Dystrophy Type 1“. International Journal of Molecular Sciences 19, Nr. 12 (18.12.2018): 4104. http://dx.doi.org/10.3390/ijms19124104.
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Myotonic dystrophy type 1 (DM1), the most common cause of adult-onset muscular dystrophy, is autosomal dominant, multisystemic disease with characteristic symptoms including myotonia, heart defects, cataracts and testicular atrophy. DM1 disease is being successfully modelled in Drosophila allowing to identify and validate new pathogenic mechanisms and potential therapeutic strategies. Here we provide an overview of insights gained from fruit fly DM1 models, either: (i) fundamental with particular focus on newly identified gene deregulations and their link with DM1 symptoms; or (ii) applied via genetic modifiers and drug screens to identify promising therapeutic targets.
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Day, J. W., K. Ricker, J. F. Jacobsen, L. J. Rasmussen, K. A. Dick, W. Kress, C. Schneider et al. „Myotonic dystrophy type 2“. Neurology 60, Nr. 4 (25.02.2003): 657–64. http://dx.doi.org/10.1212/01.wnl.0000054481.84978.f9.
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Background: Myotonic dystrophy types 1 (DM1) and 2 (DM2/proximal myotonic myopathy PROMM) are dominantly inherited disorders with unusual multisystemic clinical features. The authors have characterized the clinical and molecular features of DM2/PROMM, which is caused by a CCTG repeat expansion in intron 1 of the zinc finger protein 9 (ZNF9) gene.Methods: Three-hundred and seventy-nine individuals from 133 DM2/PROMM families were evaluated genetically, and in 234 individuals clinical and molecular features were compared.Results: Among affected individuals 90% had electrical myotonia, 82% weakness, 61% cataracts, 23% diabetes, and 19% cardiac involvement. Because of the repeat tract’s unprecedented size (mean ∼5,000 CCTGs) and somatic instability, expansions were detectable by Southern analysis in only 80% of known carriers. The authors developed a repeat assay that increased the molecular detection rate to 99%. Only 30% of the positive samples had single sizeable expansions by Southern analysis, and 70% showed multiple bands or smears. Among the 101 individuals with single expansions, repeat size did not correlate with age at disease onset. Affected offspring had markedly shorter expansions than their affected parents, with a mean size difference of −17 kb (−4,250 CCTGs).Conclusions: DM2 is present in a large number of families of northern European ancestry. Clinically, DM2 resembles adult-onset DM1, with myotonia, muscular dystrophy, cataracts, diabetes, testicular failure, hypogammaglobulinemia, and cardiac conduction defects. An important distinction is the lack of a congenital form of DM2. The clinical and molecular parallels between DM1 and DM2 indicate that the multisystemic features common to both diseases are caused by CUG or CCUG expansions expressed at the RNA level.
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Neault, Nafisa, Aymeric Ravel-Chapuis, Stephen D. Baird, John A. Lunde, Mathieu Poirier, Emiliyan Staykov, Julio Plaza-Diaz et al. „Vorinostat Improves Myotonic Dystrophy Type 1 Splicing Abnormalities in DM1 Muscle Cell Lines and Skeletal Muscle from a DM1 Mouse Model“. International Journal of Molecular Sciences 24, Nr. 4 (14.02.2023): 3794. http://dx.doi.org/10.3390/ijms24043794.
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Myotonic dystrophy type 1 (DM1), the most common form of adult muscular dystrophy, is caused by an abnormal expansion of CTG repeats in the 3′ untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. The expanded repeats of the DMPK mRNA form hairpin structures in vitro, which cause misregulation and/or sequestration of proteins including the splicing regulator muscleblind-like 1 (MBNL1). In turn, misregulation and sequestration of such proteins result in the aberrant alternative splicing of diverse mRNAs and underlie, at least in part, DM1 pathogenesis. It has been previously shown that disaggregating RNA foci repletes free MBNL1, rescues DM1 spliceopathy, and alleviates associated symptoms such as myotonia. Using an FDA-approved drug library, we have screened for a reduction of CUG foci in patient muscle cells and identified the HDAC inhibitor, vorinostat, as an inhibitor of foci formation; SERCA1 (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) spliceopathy was also improved by vorinostat treatment. Vorinostat treatment in a mouse model of DM1 (human skeletal actin–long repeat; HSALR) improved several spliceopathies, reduced muscle central nucleation, and restored chloride channel levels at the sarcolemma. Our in vitro and in vivo evidence showing amelioration of several DM1 disease markers marks vorinostat as a promising novel DM1 therapy.
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Mahadevan, Mani S., Ramesh S. Yadava und Mahua Mandal. „Cardiac Pathology in Myotonic Dystrophy Type 1“. International Journal of Molecular Sciences 22, Nr. 21 (02.11.2021): 11874. http://dx.doi.org/10.3390/ijms222111874.
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Myotonic dystrophy type 1 (DM1), the most common muscular dystrophy affecting adults and children, is a multi-systemic disorder affecting skeletal, cardiac, and smooth muscles as well as neurologic, endocrine and other systems. This review is on the cardiac pathology associated with DM1. The heart is one of the primary organs affected in DM1. Cardiac conduction defects are seen in up to 75% of adult DM1 cases and sudden death due to cardiac arrhythmias is one of the most common causes of death in DM1. Unfortunately, the pathogenesis of cardiac manifestations in DM1 is ill defined. In this review, we provide an overview of the history of cardiac studies in DM1, clinical manifestations, and pathology of the heart in DM1. This is followed by a discussion of emerging data about the utility of cardiac magnetic resonance imaging (CMR) as a biomarker for cardiac disease in DM1, and ends with a discussion on models of cardiac RNA toxicity in DM1 and recent clinical guidelines for cardiologic management of individuals with DM1.
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Ballester-Lopez, Alfonsina, Judit Núñez-Manchón, Emma Koehorst, Ian Linares-Pardo, Miriam Almendrote, Giuseppe Lucente, Nicolau Guanyabens et al. „Three-dimensional imaging in myotonic dystrophy type 1“. Neurology Genetics 6, Nr. 4 (21.07.2020): e484. http://dx.doi.org/10.1212/nxg.0000000000000484.
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ObjectiveWe aimed to determine whether 3D imaging reconstruction allows identifying molecular:clinical associations in myotonic dystrophy type 1 (DM1).MethodsWe obtained myoblasts from 6 patients with DM1 and 6 controls. We measured cytosine-thymine-guanine (CTG) expansion and detected RNA foci and muscleblind like 1 (MBNL1) through 3D reconstruction. We studied dystrophia myotonica protein kinase (DMPK) expression and splicing alterations of MBNL1, insulin receptor, and sarcoplasmic reticulum Ca(2+)-ATPase 1.ResultsThree-dimensional analysis showed that RNA foci (nuclear and/or cytoplasmic) were present in 45%–100% of DM1-derived myoblasts we studied (range: 0–6 foci per cell). RNA foci represented <0.6% of the total myoblast nuclear volume. CTG expansion size was associated with the number of RNA foci per myoblast (r = 0.876 [95% confidence interval 0.222–0.986]) as well as with the number of cytoplasmic RNA foci (r = 0.943 [0.559–0.994]). Although MBNL1 colocalized with RNA foci in all DM1 myoblast cell lines, colocalization only accounted for 1% of total MBNL1 expression, with the absence of DM1 alternative splicing patterns. The number of RNA foci was associated with DMPK expression (r = 0.967 [0.079–0.999]). On the other hand, the number of cytoplasmic RNA foci was correlated with the age at disease onset (r = −0.818 [−0.979 to 0.019]).ConclusionsCTG expansion size modulates RNA foci number in myoblasts derived from patients with DM1. MBNL1 sequestration plays only a minor role in the pathobiology of the disease in these cells. Higher number of cytoplasmic RNA foci is related to an early onset of the disease, a finding that should be corroborated in future studies.
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Bérenger-Currias, Noémie, Cécile Martinat und Sandrine Baghdoyan. „Pluripotent Stem Cells in Disease Modeling and Drug Discovery for Myotonic Dystrophy Type 1“. Cells 12, Nr. 4 (10.02.2023): 571. http://dx.doi.org/10.3390/cells12040571.
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Myotonic dystrophy type 1 (DM1) is a progressive multisystemic disease caused by the expansion of a CTG repeat tract within the 3′ untranslated region (3′ UTR) of the dystrophia myotonica protein kinase gene (DMPK). Although DM1 is considered to be the most frequent myopathy of genetic origin in adults, DM1 patients exhibit a vast diversity of symptoms, affecting many different organs. Up until now, different in vitro models from patients’ derived cells have largely contributed to the current understanding of DM1. Most of those studies have focused on muscle physiopathology. However, regarding the multisystemic aspect of DM1, there is still a crucial need for relevant cellular models to cover the whole complexity of the disease and open up options for new therapeutic approaches. This review discusses how human pluripotent stem cell–based models significantly contributed to DM1 mechanism decoding, and how they provided new therapeutic strategies that led to actual phase III clinical trials.
Dissertationen zum Thema "Myotonic Dystrophy type 1 (DM1)"
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Minier, Lisa. „Evaluation de la personnalité, du coping et de la régulation émotionnelle de patients atteints de Dystrophie Myotonique de type 1 (DM1)“. Thesis, Paris 10, 2019. http://faraway.parisnanterre.fr/login?URL=http://bdr.parisnanterre.fr/theses/intranet/2019/2019PA100112/2019PA100112.pdf.
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Le Dystrophie Myotonique de type 1 (DM1) est une maladie neuromusculaire aux atteintes multiples qui induisent notamment de l’émoussement affectif, de l’apathie, de l’hypersomnolence, de la fatigue, ainsi qu’un déficit de cognition sociale et de théorie de l’esprit. Nous avons évalué les traits de personnalité, le coping et la régulation émotionnelle de 60 patients atteints de DM1. In fine, il s’agissait de proposer, à partir de ces éléments, une prise en charge psychothérapeutique adaptée à leurs besoins. Concernant la personnalité, le résultat le plus frappant concerne la dimension N. Contrairement à ce que nous attendions (des scores élevés du fait de la maladie et de ses répercussions), les patients inclus dans notre échantillon obtiennent des scores similaires à ceux de notre groupe contrôle tout-venant. Nos résultats relatifs au coping témoignent d’une utilisation variée des 10 stratégies que nous avons évaluées. Toutefois, l’apathie et la motivation réduite ressortent comme des obstacles qui limiteraient leur mise en place pour faire face à la DM1. Enfin, l’apathie et la fatigue ne semblent pas influencer la régulation émotionnelle dans notre échantillon. De plus, la stratégie Réévaluation cognitive ne semble pas être impactée par la maladie, ce qui pourrait se révéler un atout important dans la préservation de la qualité de vie des patients malgré la progression de leurs atteintes. En termes de psychothérapie, une Thérapie Comportementale et Cognitive a été développée spécifiquement pour ces patients et apporte des résultats prometteurs. D’autres pistes de psychothérapies pourraient être intéressantes à explorer, notamment la thérapie d’acceptation et d’engagementMyotonic Dystrophy type 1 (DM1) is a neuromuscular disease with multiple impairments leading to blunted affect, apathy, hypersomnia, fatigue, social cognition deficit and theory of mind deficit. In this research, personality traits, coping, and emotion regulation of 60 DM1 patients were assessed. All this information will help us design DM1 adapted psychological care.Regarding personality, our main result is that patients show similar N scores to the healthy control group despite our expectations (high scores in relation with the severity of the disease and its complications). In the light of our coping results, it seems that DM1 patients are using a large variety of coping strategies. However, apathy and reduced motivation constitute obstacles for coping strategies. Finally, apathy and fatigue do not influence emotion regulation in our sample DM1. Furthermore, Cognitive reevaluation strategy seems preserved from the disease’s consequences. This strategy might be an important advantage in the preservation of quality of life in DM1, despite the disease progression. A DM1 specific Cognitive Behavioral Therapy showed promising results. Other psychotherapeutic approaches could be explored, namely Acceptance and Commitment Therapy
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De, Dea Diniz Damily. „The study of the consequences of serca1’s missplicing on muscle function in myotonic dystrophy type 1“. Electronic Thesis or Diss., Sorbonne université, 2018. http://www.theses.fr/2018SORUS569.
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La Dystrophie myotonique de type 1 (DM1) est une maladie neuromusculaire affectant notamment le muscle squelettique avec la présence d’une myotonie et d’une atrophie progressive et causée par une expansion anormale de triplets CTG dans le 3’UTR du gène DMPK. L’expression des ARN mutés induit la perte de fonction du facteur d’épissage MBNL1 et conduit à la réexpression de formes fœtales de certains transcrits dans les tissus adultes de patients DM1. J’ai développé un modèle de cellules musculaires exprimant de manière conditionnelle de 960 répétitions CTG interrompues, afin d’identifier des nouveaux mécanismes impliqués dans la dysfonction musculaire. Suite à l’expression ciblée d’ARN-960CUG dans des myotubes, une analyse du transcriptome montre la présence d’un certain nombre de fonction/processus biologiques typiques de la DM1. En revanche, l’induction de voies non associées à la DM1 et l’absence de phénotype suggèrent que notre modèle n’est pas approprié pour l’étude des mécanismes moléculaires. J’ai fait aussi une étude de l’impact du défaut d’épissage d’ATP2A1 (SERCA1), présent chez les patients DM1, sur la fonction musculaire. J’ai utilisé une approche antisens afin de favoriser l’exclusion de l’exon 22 d’Atp2a1 dans un muscle contrôle, conduisant à la réexpression de l’isoforme fœtal Serca1b. Chez la souris sauvage adulte, ce défaut provoque un ralentissement de la contraction et une perte de masse musculaire. Chez le poisson-zèbre, cette modification d’épissage provoque une altération de la locomotion. L’ensemble de ces résultats indique que la réexpression de Serca1b affecte la fonction musculaire et pourrait contribuer aux symptômes musculaires dans la DM1Myotonic Dystrophy Type 1 (DM1) is a neuromuscular disease that affects mainly the skeletal muscle with the presence of myotonia and progressive atrophy and is caused by abnormal CTG expansion in the 3'UTR of the DMPK gene. The expression of the mutated RNA induces the loss of function of the MBNL1 splicing factor and leads to the re-expression of fetal isoforms of certain transcripts in the adult tissues of DM1 patients. In order to identify new mechanisms involved in muscle dysfunction, I developed a model of muscle cells conditionally expressing 960 interrupted CTG repeats. Following the targeted expression of RNA-960CUG in myotubes, transcriptome analysis shows that despite the presence of functions/biological processes typical of DM1, the induction of non-DM1 associated pathways and the absence of phenotype suggest that this model is not appropriate for this study of molecular mechanisms. I also did a study of the impact of the ATP2A1 (SERCA1) misplicing, present in DM1 patients, on the muscular function. I used an antisense approach to promote the exclusion of exon 22 from Atp2a1 in the muscle of two animal models, leading to the reexpression of the Serca1b fetal isoform. The re-expression of Serca1b in the muscle of adult wild-type mice leads to a slowing contraction and a loss of muscle mass. In zebrafish, this modification on Atp2a1 splicing causes an alteration on the locomotion. All of these results indicate that reexpression of Serca1b affects muscle function and may contribute to muscle symptoms in DM1
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Lallemant, Louison. „Pathologie neuronale et gliale en lien avec les atteintes neurologiques de la dystrophie myotonique de type 1 (DM1)“. Electronic Thesis or Diss., Sorbonne université, 2023. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2023SORUS404.pdf.
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La dystrophie myotonique de type 1 (DM1) est une maladie neuromusculaire grave affectant de nombreux tissus et organes. Les manifestations neurologiques varient du dysfonctionnement exécutif chez les adultes aux déficits d'attention chez les enfants, en passant par une déficience intellectuelle sévère dans les cas congénitaux. Les manifestations neurologiques de la DM1 ont un impact important sur la vie quotidienne des patients et de leurs familles, et il n’existe actuellement aucun traitement pour cette maladie. La DM1 est causée par l'expansion anormale d'une répétition CTG dans le gène DMPK. Les transcrits DMPK mutés sont toxiques car ils s’accumulent dans le noyau de la cellule, perturbant l’activité d’importantes protéines de liaison à l’ARN. En conséquence, les cellules DM1 présentent un métabolisme anormal de l’ARN et une régulation anormale de nombreux transcrits en aval. Malgré les progrès dans la compréhension de la physiopathologie musculaire, les mécanismes de la maladie restent flous et méconnus dans le SNC. Nous ne savons toujours pas quels types de cellules et voies moléculaires sont principalement affectés dans le cerveau, ni comment ils contribuent aux symptômes neurologiques de la DM1. Afin d'étudier ce problème, notre laboratoire a développé un modèle murin transgénique de la DM1 : les souris DMSXL expriment des transcrits DMPK humain contenant plus de 1000 répétitions CUG dans plusieurs tissus, notamment dans le cerveau. Ces souris présentent des phénotypes comportementaux, électrophysiologiques et neurochimiques pertinents de la DM1. A l'aide de ce modèle murin, l'objectif de ma thèse était de mieux comprendre les mécanismes cellulaires et moléculaires impliqués dans les anomalies neuronales, mais aussi non neuronales liées aux atteintes neurologiques de la DM1. Je me suis d'abord concentrée sur la caractérisation des différents types cellulaires du cerveau des souris DMSXL. Une étude multi-omique a été réalisée sur les neurones, les astrocytes et les oligodendrocytes ces souris. Nos résultats, qui montrent que les cellules gliales sont davantage impactées par les répétitions CTG, ont permis de mieux comprendre les mécanismes cellulaires et moléculaires de la DM1 dans le SNC, mais surtout de souligner l'importance d'étudier non seulement les neurones, mais aussi les astrocytes et oligodendrocytes dans le contexte pathologique de la DM1. Je me suis ensuite impliquée dans l'étude de la pathologie des astrocytes dans la DM1. Nous avons ainsi démontré que les astrocytes DMSXL présentaient une ramification réduite et une adhésion cellulaire altérée, et avaient un fort impact négatif sur la neuritogenèse. Parallèlement, j'ai également participé à l'étude de l'altération oligodendrogliale dans la DM1. Nous avons constaté que l'ARN CUG toxique perturbe le programme moléculaire de différenciation des oligodendrocytes (OL), en association avec des modifications du transcriptome se produisant au cours de la transition des cellules progénitrices des oligodendrocytes (OPC) en OL et conduisant à une hypomyélinisation transitoire chez la souris. J'ai également étudié la pathologie neuronale chez la souris DMSXL. Nos résultats ont démontré que l’accumulation de foci d’ARN toxiques dans les neurones perturbe principalement la phosphorylation des protéines, ce qui semble conduire à des défauts morphologiques neuronaux associés à des troubles de la dynamique des vésicules et à des défauts de transport axonal.Les 3 types cellulaires du cerveau présentent donc des dommages importants dans le cadre de la DM1, qui pourraient avoir un impact sur des processus cruciaux du fonctionnement cérébral. En effet, nous avons démontré une altération de la neurotransmission et de la plasticité synaptique chez la souris DMSXL. Dans l'ensemble, mes travaux ont permis de mieux comprendre les mécanismes cellulaires et moléculaires spécifiques des astrocytes, des oligodendrocytes et des neurones dans la pathologie cérébrale de la DM1Myotonic dystrophy type 1 (DM1) is a severe neuromuscular disease affecting many tissues and organs. The debilitating neurological manifestations vary from executive dysfunction in adults, to attention deficits and low processing speed in pediatric patients, to severe intellectual disability in congenital cases. DM1 neurological manifestations have a profound impact on the daily life of patients and their families, and there is currently no treatment for this disease. DM1 is caused by the abnormal expansion of a CTG repeat in DMPK gene. Expanded DMPK transcripts are toxic because they accumulate in the cell nucleus, disrupting the activity of important RNA-binding proteins. As a consequence, DM1 cells show abnormal RNA metabolism and processing of many downstream transcripts. Despite progress in the understanding of the muscle pathophysiology, the disease mechanisms remain unclear in the CNS. We still do not know which cell types and molecular pathways are primarily affected in the brain and how they contribute to DM1 neurological symptoms. In order to investigate this problem, our laboratory has developed a transgenic mouse model of DM1: DMSXL mice express expanded human DMPK transcripts in multiple tissues, notably in the brain, and display relevant behavioral, electrophysiological and neurochemical phenotypes. Using this mouse model, the objective of my thesis was to better understand the cellular and molecular mechanisms involved in the neuronal and non-neuronal impairment linked to the neurological damages of DM1. I first focused on the characterization of the different cell types in the DMSXL brain. A multi-omics study was carried out on DMSXL neurons, astrocytes and oligodendrocytes. Our results, which show that glial cells are more impacted by CTG repeats, have allowed us to better understand the cellular and molecular mechanisms of DM1 in the CNS, but above all to emphasize the importance of studying not only the neurons, but also astrocytes and oligodendrocytes in the pathological context of DM1. I then got involved in the study of astrocyte pathology in DM1. We thus demonstrated that DMSXL astrocytes exhibited reduced ramification and impaired cell adhesion, and had a strong negative impact on neuritogenesis. In the same time, I also participated in the study of oligodendroglia impairment in DM1. We found that the toxic CUG RNA disrupts the molecular program of oligodendrocyte (OL) differentiation, impairing the transcriptome changes occurring during the oligodendrocyte precursor cells (OPC)-OL transition and leading to transient hypomyelination in mice. I also studied the neuronal pathology in DMSXL mice. Our results demonstrated that the accumulation of toxic RNA foci in neurons perturbs mainly protein phosphorylation, which seems to lead to neuronal morphological defects associated with vesicle dynamics impairment and axonal transport defects. The three main cell types of the brain therefore present significant damage in the context of DM1, which could have an impact on crucial processes of cerebral functioning. Indeed, we have demonstrated an alteration in neurotransmission and synaptic plasticity in DMSXL mice. All together my work has provided novel insight into the cell-specific mechanisms operating in DM1, demonstrating the implication of astrocyte, oligodendrocyte and neuron defects in a DM1mouse model, and contributing towards an integrative understanding of brain pathology
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Vergnol, Amélie. „Les isoformes CaVβ1 : rôle dans la formation de la jonction neuromusculaire et implication dans la physiopathologie de la Dystrophie Myotonique de type 1“. Electronic Thesis or Diss., Sorbonne université, 2024. http://www.theses.fr/2024SORUS305.
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Quatre protéines CaVβ (CaVβ1 à CaVβ4) sont connues comme des sous-unités régulatrices des canaux Ca2+ dépendants du voltage (Voltage-gated Ca2+ Channels, VGCC), chacune ayant des profils d'expression spécifiques selon leur fonction. Bien qu'elles soient principalement reconnues pour leur rôle dans la régulation des VGCC, les protéines CaVβ peuvent également agir indépendamment de ces canaux, en tant que régulateurs de l'expression génique. Parmi ces protéines, CaVβ1 est exprimée dans le muscle squelettique sous différentes isoformes. L'isoforme adulte constitutive, CaVβ1D, est localisée au niveau du sarcolemme et plus précisément à la triade, où elle joue un rôle crucial dans la régulation de CaV1 et ainsi du mécanisme de Couplage Excitation-Contraction (CEC), essentiel à la contraction musculaire. Dans cette thèse, nous nous sommes concentrés sur les isoformes embryonnaires/périnatales de CaVβ1, moins étudiées, y compris la CaVβ1E précédemment décrite. Nous avons étudié leurs rôles dans les systèmes neuromusculaire et musculaire. En effet, la protéine CaVβ1 s'est révélée essentielle au développement correct de la Jonction NeuroMusculaire (JNM), mais l'implication spécifique de ses isoformes y reste inconnue. Notre étude a donc évalué le rôle des isoformes CaVβ1 à différents stades de la formation et de la maturation/maintien de la JNM. Parallèlement, étant donné la dérégulation de CaVβ1 dans la dystrophie myotonique de type 1 (DM1), nous avons exploré son rôle fonctionnel dans ce contexte pathologique. Nous avons tout d'abord identifié CaVβ1A comme une isoforme exprimée pendant l'embryogenèse et les stades périnataux. Nos résultats ont révélé que l'expression des isoformes CaVβ1 est régulée par l'activation différentielle des promoteurs au cours du développement : un promoteur1 dans l'exon 1 contrôle l'expression de CaVβ1A/E, tandis qu'un promoteur2 dans l'exon 2B contrôle l'expression de CaVβ1D. Il est intéressant de noter qu'un endommagement du nerf déclenche une réactivation du promoteur1, conduisant à la réexpression des transcrits de CaVβ1A/E.De plus, nous avons découvert que les isoformes embryonnaires/périnatales de CaVβ1 sont essentielles pour la pré-empreinte in vitro des myotubes et que leur expression postnatale influence la maturation/maintien de la JNM. Dans le contexte pathologique de la DM1, nous avons observé une augmentation de l'expression de CaVβ1A/E, qui semble atténuer la myotonie, un symptôme caractéristique de cette pathologie. De plus, nous avons trouvé que la modulation de leur expression est liée aux protéines MBNL, centrales dans la physiopathologie de la DM1. En conclusion, ce travail de thèse a permis de clarifier les connaissances sur les différentes isoformes de CaVβ1 dans le muscle squelettique et d'apporter de nouveaux éléments sur leur rôle dans deux contextes indépendants : le développement de la JNM et de la physiopathologie de la DM1. Comprendre la régulation des isoformes protéiques de CaVβ1 dans le muscle squelettique est essentiel pour déchiffrer les mécanismes de l'homéostasie musculaire et potentiellement identifier de nouvelles approches thérapeutiques pour faire face aux pathologies musculairesFour CaVβ proteins (CaVβ1 to CaVβ4) are described as regulatory subunit of Voltage-gated Ca2+ channel (VGCC), each exhibiting specific expression pattern in excitable cells based on their function. While primarily recognized for their role in VGCC regulation, CaVβ proteins also function independently of channels, acting as regulators of gene expression. Among these, CaVβ1 is expressed in skeletal muscle as different isoforms. The adult constitutive isoform, CaVβ1D, is located at the sarcolemma and more specifically at the triad, where it plays a crucial role in regulating CaV1 to control Excitation-Contraction Coupling (ECC) mechanism, essential for muscle contraction.In this thesis, we further explored the less studied CaVβ1 isoforms, with a particular focus on embryonic/perinatal variants, including the previously described CaVβ1E. We investigated their roles in the neuromuscular and muscular systems. Indeed, CaVβ1 proteins have been showed as essential for NeuroMuscular Junction (NMJ) development, though the involvement of specific isoform remains unclear. Our investigation assessed the role of CaVβ1 isoforms at different stages of NMJ formation and maturation/maintenance. Additionally, given the deregulation of CaVβ1 in Myotonic Dystrophy Type 1 (DM1), we explored its functional role in this muscular pathological context.First, we identified CaVβ1A as another isoform expressed during embryogenesis and perinatal stages. Our findings revealed that CaVβ1 isoforms expressions are regulated by the differential activation of promoters during development: a promoter1 in exon 1 drives CaVβ1A/E expressions, while a promoter2 in exon 2B controls CaVβ1D expression. Interestingly, nerve damage in adult muscle triggers a shift toward the promoter1 activation and leading to the re-expression of CaVβ1A/E transcripts. Furthermore, we found that CaVβ1 embryonic/perinatal isoforms are critical for proper in vitro pre-patterning of myotubes and that their postnatal expressions influences NMJ maturation/maintenance. In the pathological context of DM1, we observed the increased expression of CaVβ1A/E, which appears to mitigate myotonia symptoms. In addition, we found that the modulation of their expression is linked with MBNL proteins, which are central in the pathophysiology of DM1. In conclusion, this thesis work has clarified knowledge of the various CaVβ1 isoforms in skeletal muscle and provides new insights into their role in two independent contexts of NMJ development and DM1 pathophysiology. Understanding CaVβ1 protein regulation in skeletal muscle is essential to decipher muscle homeostasis mechanisms and potentially identify new therapeutic targets to face muscular disorders
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Ney, Michel. „Rôle de l'inclusion de l'exon 7 de BIN1 dans la faiblesse musculaire des patients atteints de dystrophie myotonique“. Thesis, Strasbourg, 2016. http://www.theses.fr/2016STRAJ077/document.
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La dystrophie myotonique de type 1 (DM1), est une maladie génétique héréditaire affectant environ 1/8000 personnes. Les patients souffrant de DM1 développent essentiellement des troubles musculaires tels qu’une faiblesse et une atrophie musculaire. La cause de la DM1 est expliquée par la mutation du gène "DMPK". Lors de ma thèse, j’ai pu démontrer que l’épissage de l’ARNm BIN1 était altéré dans le muscle DM1. En effet, l’exon 7 de BIN1, qui est absent du muscle normal, est exprimé de façon aberrante chez les patients DM1. En utilisant un modèle murin, j’ai prouvé que l’expression forcée de l’exon 7 de BIN1 altérait simultanément la structure et la fonction du muscle. Nous avons notamment observés une diminution de la taille des fibres musculaires et une augmentation de la faiblesse musculaire, comparé à des souris normales. Par conséquent, ce travail aidera à la compréhension du mécanisme de la maladie et pourrait expliquer les causes de la faiblesse musculaire et de l’atrophieMyotonic dystrophy of type 1 (DM1), is an inherited genetic disease affecting around 1 in 8000 person. Patients suffering from DM1 develop essentially muscle disorders such as muscle weakness, muscle loss and atrophy. The cause of DM1 is explained by the mutation of a gene called “DMPK“.During my thesis, I discovered that the alternative splicing of BIN1 mRNA was altered in the muscle of DM1 patients. Indeed, the BIN1 exon 7, which is normally absent in healthy muscle, is aberrantly expressed in DM1 muscle. By using a mouse model, I found that the forced expression of BIN1 exon 7 was responsible of the alteration of both muscle structure and function. Notably, we found a decrease in muscle fibers area (atrophy) and an increase of muscle weakness, compared to wild-type mice. Therefore, this work will help in the understanding of the disease mechanism and could explain the causes of muscle weakness and atrophy, which have never been elucidated to this date
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Winblad, Stefan. „Myotonic dystrophy type 1 : cognition, personality and emotion /“. Göteborg : Göteborg University, Dept. of Psychology, 2006. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=015464022&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
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Haworth, Christine. „Understanding the pathogenesis of myotonic dystrophy type 1“. Thesis, University of Glasgow, 2008. http://theses.gla.ac.uk/478/.
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To identify the full range of targets and the pathogenic consequences, we sought to mimic the pathogenesis of myotonic dystrophy type 1 with temporal and spatial control: temporal to reproduce the developmental pathogenesis of the congenital form, and spatial to isolate tissue specific pathology. To do this, we attempted to use the Cre-lox system for the conditional expression of an EGFP reporter-linked expanded CUG repeat RNA in the mouse. Expression of the transgene was controlled by Cre excision of a transcriptional stop, placed upstream of the EGFP-expanded repeat open reading frame. The transgenes were constructed and tested successfully, and a normal length repeat transgenic line was established. Unfortunately generation of the expanded repeat line was not successful. The constructs were used to generate cell-culture models of DM1, in both human and murine cells, which mimicked the nuclear foci formation and MBNL1 co-localisation seen in patient cells. Expression of exogenous MBNL1/GFP fusion protein in this model resulted in an increase in the size of foci, indicating that MBNL1 protein is limiting within the cell, and may possibly play a protective role. The murine DM1 cell-culture model was used to investigate the effects of expanded CUG repeat expression on splicing within the transcriptome. The differential effect between 5 and 250 repeat RNA expression using Affymetrix whole transcript and exon arrays was compared. Using whole genome arrays, 6 genes were down-regulated and 128 upregulated. With exon arrays, 58 genes showed alternative exon usage. Six genes were selected for further bioinformatics analysis: MtmR4, which has possible neuromuscular involvement; Kcnk4, Narg1, Ttyh1 and Bptf, potentially related to brain development; and Cacna1c, a promising candidate for heart conductance defects and sudden death.
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Osborne, Robert J. „Caenorhabditis elegans models of myotonic dystrophy type 1“. Thesis, University of Nottingham, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.408632.
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Langlois, Marc-André. „RNA-based gene therapies for myotonic dystrophy type 1“. Thesis, Université Laval, 2003. http://www.theses.ulaval.ca/2003/21404/21404.pdf.
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La dystrophie myotonique de type 1 (DM1) est une maladie neuromusculaire grave qui engendre une perte d’autonomie des patients et diminue leur espérance de vie. Cette maladie est la plus fréquente des dystrophies musculaires chez l’adulte avec une incidence mondiale d’une personne atteinte sur 15 000. Au Québec, cette maladie est d’une importance particulière, car elle touche une personne sur 500 dans les régions du Saguenay et de Charlevoix. La DM1 est causée par l’expansion du triplet CTG situé dans la région 3’ non-codante de la myotonine protéine kinase (DMPK). Toutefois, il a été démontré que la grande part des symptômes de la maladie seraient liés à l’accumulation nucléaire de l’ARNm de DMPK portant l’expansion. Ces ARNm mutés se lient à des facteurs nucléaires formant des foci dans les noyaux des cellules DM1, engendrant des effets toxiques sur le métabolisme cellulaire et sur l’épissage alternatif de certains ARNm.
Nos travaux avaient comme but premier d’évaluer si la destruction de l’ARNm mutant de DMPK dans des myoblastes provenant de muscle squelettique DM1 permettrait de rétablir certaines fonctions et caractéristiques normales dans ces cellules. Trois technologies à base d’ARNs: les antisens, les ribozymes et les shRNAs ont diminué avec succès ces niveaux d’ARN mutés. Les ARNs antisens et les ribozymes, contrairement aux shRNA, ont permis un ciblage préférentiel des ARNs mutés de DMPK dans le noyau de myoblastes DM1. Ceci permet donc de maintenir un niveau basal de la protéine DMPK dans les myoblastes, un détail important advenant l’utilisation de ces molécules en thérapie génique chez l’humain. En utilisant les ribozymes, nous avons diminué la quantité et l’intensité des foci ce qui a permis de libérer les facteurs cellulaires se liant aux expansions de CUG. Ceci a eu comme effet de corriger un défaut d’épissage alternatif dans le récepteur à l’insuline. En exprimant de longs antisenses à l’ARNm de DMPK par un oncorétrovirus, nous avons constaté une restauration de la fusion cellulaire, de la capture de glucose ainsi qu’une diminution de CUGBP, un facteur d’épissage alternatif. Nous avons également démontré que la surexpression de hnRNP H, un facteur d’épissage liant les expansions de CUG, permettait aussi de diminuer les niveaux de CUGBP et ainsi corriger le défaut d’épissage alternatif du récepteur à l’insuline. Ces résultats démontrent donc pour la première fois le lien direct entre la rétention des ARNs mutés, la déplétion nucléaire d’un facteur d’épissage s’y liant et l’exacerbation de certaines caractéristiques du phénotype DM1. La somme de nos observations a permis deux choses importantes: en premier lieu, d’établir un nouveau modèle détaillé expliquant la pathogenèse de la DM1. En second lieu, nos résultats ont permi de valider la pertinence de détruire spécifiquement les transcrits mutés de DMPK afin de développer une thérapie génique efficace pour la DM1.Myotonic dystrophy type 1 (DM1) is a severe neuromuscular disease that ultimately causes loss of mobility and premature death. DM1 is the most common muscular dystrophy in adults with a world wide incidence of 1 affected individual in every 15 000. This disease is of special relevance in the Saguenay and Charlevoix regions in Quebec, where 1 in every 500 individuals is a carrier of the mutation. DM1 is caused by the expansion of an unstable CTG trinucleotide repeat located in 3’UTR of the DMPK (DM protein kinase) gene. However, it has been shown that most DM1 symptoms are related to the nuclear retention of mutant DMPK mRNA. These mutant transcripts bind to nuclear proteins and form foci in DM1 cell nuclei. This is though to be the leading cause of metabolical disruptions and defective alternative splicing of several mRNAs observed in DM1 cells. Our main project objective was to evaluate whether destruction of mutant DMPK mRNA could restore normal phenotype features in DM1 human skeletal myoblasts. The use of three RNA-based approaches: antisense RNAs, ribozymes and shRNAs, all displayed significant reductions in mutant DMPK mRNA. Antisense RNAs and ribozymes, as opposed to shRNAs, allowed specific targeting and destruction of mutant DMPK mRNAs in the nucleus of DM1 myoblasts. This feature thus allows a basal level of DMPK protein expression which is of particular relevance in the advent of developing a gene therapy for DM1. Ribozymes were effective in reducing the number and intensity of foci present in the nucleus of the myoblasts, thus allowing the release of certain CUG-binding proteins. This resulted in restoration of the defective splicing of the insulin receptor mRNA. Antisense RNAs to the DMPK mRNA expressed by an oncoretrovirus restored myoblast fusion, glucose uptake and lowered nuclear levels of CUGBP, an alternative splicing factor. Over expression of hnRNP-H, an alternative splicing factor that we showed could bind to CUG repeats, also reduces expression of CUGBP and restores defective splicing of the insulin receptor. These results reveal for the first time the intricate link between mutant DMPK mRNA nuclear retention, depletion of a CUG-binding protein that is also a splicing factor and exacerbation of related DM1 features. In conclusion, our work has allowed to better define the mechanisms involved in DM1 pathogenesis and has validated the relevance of developing a gene therapy that specifically targets mutant DMPK mRNAs.
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Nasser, Khalidah K. „Genetic and symptomatic variations in Myotonic Dystrophy Type 1“. Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/7874/.
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Myotonic dystrophy type 1 (DM1) is an extremely variable genetic disorder showing an autosomal dominant inheritance that is characterised by myotonia, insulin resistance, cardiac conduction defects and cataracts. It is caused by a trinucleotide repeat expansion of CTG sequence located in the 3’-untranslated region of the dystrophia myotonica-protein kinase (DMPK) gene on chromosome 19 at q13.3. The severity of symptoms ranges from mild adult onset to severe congenital form. A characteristic clinical feature of DM1 is anticipation phenomenon where disease severity increases and age of onset decreases over successive generations. The DM1 mutation is highly unstable in both the germline and soma, and showed to be an age-dependent, tissue-specific (skeletal muscles comprised the largest allele length of approximately thousand units) and expansion biased. The unaffected level of the repeat sequence falls between ~5-37 repeats whereas the disease associated range starts from ~50 repeats, reaching several thousand units. These properties account for the observed anticipation and contribute toward the tissue-specificity and progressive nature of the symptoms. The manifested phenotypes, symptoms severity and age at onset are extremely variable within and between families. This is mostly accounted for by the progenitor allele length (PAL) passed on from affected parents in addition to the level of somatic instability over time. Though, recent data have shown that additional sequence variations (CCG, CGG variant repeats) within the repeat and immediate flanking DNA are associated with additional symptomatic variation, modified stability and delayed age of onset. Furthermore, individual specific genetic factors have shown to be clustered within and between families as a heritable trait. Therefore, it has been verified that PAL, in addition to individual specific genetic variations are the main modifier of disease onset. More recently, it has been observed that mismatch repair (MMR) genes play a key role in modulating the dynamic of DM1 mutation, and subsequently impact on the age at onset. Therefore, these genes serve as powerful trans-acting modifiers of repeat instability and subsequent severity. Also, sequestration and up-regulation of RNA binding proteins (MBNL1, CELF1 respectively) against the trapped mutant transcripts are the hall mark of DM1 pathogenicity associated with alternative splicing defects that account for the variability of symptoms. Thus, sequence variations within these genes may underlie the genetic and phenotypic variability among DM1 patients. The current diagnostic test for DM1 only provides a qualitative value, and takes no account of the somatic instability and/or the presence of variations within or elsewhere in the genome. Thus, limited prognostic information is delivered to patients and their families. Although more elaborate genotyping approaches that measure the DM1 degree of instability was developed, they remain labour intensive, time consuming and are not suited to routine clinical diagnostics. In this project, we have evaluated the utility of more rapid and higher throughput next generation sequencing (NGS) technologies (Ion PGM and PacBio platforms) to simultaneously sequence the DM1 alleles of the Scottish patients, characterise the immediate flanking variants (5’-extra AAT and 5’-CCG variant repeats), elucidating the possible role of these variants on the DM1 instability, and finally sequencing the potential trans-acting modifiers in a massive customised panel (Ion AmpliSeq). Though, the accurate genotyping of the DM1 allele using NGS method remains challenging and cannot be used at the moment for accurate measurement of allele length. This is due to the sequencing biased nature towards shorter fragments resulting in differences of modal allele length measurement between PacBio and traditional SP-PCR methods. Additionally, Ion PGM platform was not successful at sequencing >20 CTG repeats. To correct for the sequencing biased distribution towards shorter alleles and distinguish between possible somatic variants from sequencing errors, safe sequencing (SafeSeq) method was conducted by tagging each original parental molecule with unique identifier (UID) sequences via PCR followed by sequencing using MiSeq platform. As the UID assignment was successful in tagging different population of repeats lengths, unfortunately we were not able to confidently differentiate between true somatic mutants from possible repeat slippage events in earlier cycles of PCR. Thus, it was decided to modify the incorporation of UID sequences using ligation based approach instead of PCR, and better optimise the method for more accurate results in the future. The identification of the immediate 5’-extra AAT flanking variant of the DM1 allele in a subset of the Scottish DM1 patients with and without CCG variant repeats has led us to speculate the possible presence of a new sub derived DM1 haplotype shared by a recent common ancestor in the Scottish population. In order to address this question, we were able to discriminate the normal allele haplotype of 11-13 repeats from >20 CTG haplotype among 18 DM1 patients whom were previously sequenced by Dr. Saeed Al ghamdi. These data have illustrated the most conserved haplotype around the DM1 allele. Therefore, the corresponding region was included in a customised Ion AmpliSeq sequencing panel for future larger scale haplotype analysis, in order to provide insights about future DM1 prevalence among the Scottish population. The data of this project highlighted the importance of using NGS technologies to characterise the structural pattern of the DM1 allele containing variants that may impact on symptom severity. It also showed the successful sequencing of trans-acting genetic modifiers in massive parallel fashion. Over larger scale analysis, these data could be used for better genotype-phenotype correlation and stratify patients in future clinical trials.
Bücher zum Thema "Myotonic Dystrophy type 1 (DM1)"
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Cohen, Jeffrey A., Justin J. Mowchun, Victoria H. Lawson und Nathaniel M. Robbins. A 52-Year-Old Female with Weakness and Droopy Eyelids. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780190491901.003.0024.
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Myotonic dystrophy type 1 affects multiple organ systems and is associated with cardiac, endocrine, and ophthalmological disorders. Executive dysfunction can lead to missed appointments and an apathetic attitude, causing patients to underestimate symptoms. The findings of both clinical and electrical myotonia should suggest myotonia congenita, DM1, or DM2. Myotonic dystrophy demonstrates anticipation, where the disease has an earlier onset and more severe course with subsequent generations due to increasing trinucleotide repeats. Therefore, the diagnosis can be heralded in an adult by his/her affected child. Management of the disorder is supportive, addressing issues relating to loss of strength, cardiac conduction defects, endocrinopathies (regular monitoring with glycosylated hemoglobin and thyroid-stimulating hormone). Diagnosis and management of this disorder is discussed.
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Winblad, Stefan. Myotonic Dystrophy Type 1: Cognition, Personality and Emotion. Dept. of Psychology, Goteborg University, 2006.
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Schara, Ulrike, und Sören Lutz. „Myotone Dystrophie Typ 1 (DM1)“. In Pädiatrie, 2685–87. Berlin, Heidelberg: Springer Berlin Heidelberg, 2020. http://dx.doi.org/10.1007/978-3-662-60300-0_273.
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de Die-Smulders, Christine E. M., Frans G. I. Jennekens und Carin G. Faber. „Myotonic Dystrophy Type 1“. In Management of Genetic Syndromes, 529–46. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2010. http://dx.doi.org/10.1002/9780470893159.ch36.
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Chen, Harold. „Myotonic Dystrophy Type 1“. In Atlas of Genetic Diagnosis and Counseling, 1–13. New York, NY: Springer New York, 2015. http://dx.doi.org/10.1007/978-1-4614-6430-3_171-2.
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Oette, Mark, Marvin J. Stone, Hendrik P. N. Scholl, Peter Charbel Issa, Monika Fleckenstein, Steffen Schmitz-Valckenberg, Frank G. Holz et al. „Myotonic Dystrophy Type 1“. In Encyclopedia of Molecular Mechanisms of Disease, 1425. Berlin, Heidelberg: Springer Berlin Heidelberg, 2009. http://dx.doi.org/10.1007/978-3-540-29676-8_6375.
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Chen, Harold. „Myotonic Dystrophy Type 1“. In Atlas of Genetic Diagnosis and Counseling, 1999–2011. New York, NY: Springer New York, 2017. http://dx.doi.org/10.1007/978-1-4939-2401-1_171.
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Schara, U., und C. Schneider-Gold. „Myotone Dystrophie Typ 1 (DM1/Curschmann-Steinert-Erkrankung)“. In Klinik und Transition neuromuskulärer Erkrankungen, 129–40. Berlin, Heidelberg: Springer Berlin Heidelberg, 2014. http://dx.doi.org/10.1007/978-3-662-44239-5_20.
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Oette, Mark, Marvin J. Stone, Hendrik P. N. Scholl, Peter Charbel Issa, Monika Fleckenstein, Steffen Schmitz-Valckenberg, Frank G. Holz et al. „Myotonic Dystrophy Type 1 and Type 2“. In Encyclopedia of Molecular Mechanisms of Disease, 1425–27. Berlin, Heidelberg: Springer Berlin Heidelberg, 2009. http://dx.doi.org/10.1007/978-3-540-29676-8_1233.
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Angelini, Corrado. „Myotonic Dystrophy Type 1, Steinert Disease“. In Genetic Neuromuscular Disorders, 199–203. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-56454-8_52.
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Angelini, Corrado. „Myotonic Dystrophy Type 1, Steinert Disease“. In Genetic Neuromuscular Disorders, 167–71. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-07500-6_38.
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Schara, U., und S. Lutz. „Myotone Dystrophie Typ 1 (DM1) bei Kindern und Jugendlichen“. In Pädiatrie, 1–5. Berlin, Heidelberg: Springer Berlin Heidelberg, 2015. http://dx.doi.org/10.1007/978-3-642-54671-6_273-1.
Der volle Inhalt der QuelleKonferenzberichte zum Thema "Myotonic Dystrophy type 1 (DM1)"
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Rodbard, Gabriela Ávila, Nathália Mitsue Kishi, Renata Dal-Prá Ducci, Raphael Henrique Déa Cirino, Cláudia Suemi Kamoi Kay, Otto Jesus Hernandez Fustes, Paulo José Lorenzoni und Rosana Herminia Scola. „Non-motor symptoms and signs of Myotonic Dystrophy type 1“. In XIV Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2023. http://dx.doi.org/10.5327/1516-3180.141s1.530.
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Introduction: Myotonic Dystrophy Type 1 (DM1) is a genetic disease that presents neuromuscular manifestations and multisystemic clinical repercussions, such as cardiac and respiratory disorders, sleep disorders and impaired swallowing, among others. It is the most common muscular dystrophy in adults. Objectives: To determine the epidemiological profile of patients with DM1 treated at the Neuromuscular Diseases Outpatient Clinic of the Complexo Hospital de Clínicas da Universidade Federal do Paraná (CHC-UFPR). Methods: A total of 27 individuals diagnosed with DM1, assisted at the Neuromuscular Diseases Outpatient Clinic of the CHC-UFPR, were evaluated between May 2021 and March 2022. For this purpose, their medical records with the clinical data were analyzed. Results: The sample consisted of 78% male subjects with mean age at onset of symptoms of 27.6 ± 10.8. The most frequent muscular manifestations were myotonia (100%), weakness of the distal muscles of the upper (96.3%) and lower (96.3%) limbs, myotonic facies (92.6%). The most common non-motor manifestations were excessive daytime sleepiness (74.1%), frontal baldness (66.7%), pharyngeal globus (62.9%), choking or coughing during and/or at the end of swallowing (62.9%), cataracts (59.2%), dysphagia (55.6%), chest pain (55.6%), cognitive impairment (44.4%), dyspnea (44.4%). Of the patients, 22.2% had a previous history of pneumonia. Conclusion: The DM1 patients in this study presented an epidemiological profile consistent with that described in the literature. Non-motor manifestations are common and should be investigated, since complications such as bronchopneumonia are important causes of mortality in these patients and may negatively impact the quality of life. Therefore, DM1 patients require multidisciplinary monitoring and evaluation.
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Melone, Marie-Anne, Maxime Patout, Antoine Cuvelier, Anne-Laure Bedat-Millet, Lucie Guyant-Marechal, Alice Goldenberg, Anne-Marie Guerrot et al. „Chronic respiratory failure in myotonic dystrophy type 1 (DM1): Incidence & risk factors“. In ERS International Congress 2017 abstracts. European Respiratory Society, 2017. http://dx.doi.org/10.1183/1393003.congress-2017.pa1886.
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Holland, Ashling, Arnaud Klein, Caroline Godfrey, Niels Svenstrup, Jane Larkindale, Sonia Bracegirdle, Denis Furling und Jaya Goyal. „PGN-EDODM1: Preclinical Data Supporting the Development of an Enhanced Delivery Oligonucleotide (EDO) for the Treatment of Myotonic Dystrophy Type 1 (DM1) (S48.001)“. In 2023 Annual Meeting Abstracts. Lippincott Williams & Wilkins, 2023. http://dx.doi.org/10.1212/wnl.0000000000203804.
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Johnson, Nicholas, John Day, Johanna Hamel, Charles Thornton, S. Subramony, Payam Soltanzadeh, Jeffrey Statland et al. „Preliminary Assessment of the Phase 1/2 Clinical Trial Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AOC 1001 Administered Intravenously to Adult Patients with Myotonic Dystrophy Type 1 (DM1) (MARINA) (S48.002)“. In 2023 Annual Meeting Abstracts. Lippincott Williams & Wilkins, 2023. http://dx.doi.org/10.1212/wnl.0000000000202529.
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Mellion, Michelle, Jane Larkindale, Jennifer Cormier, Holly Hand, Sarah Vacca, Pallavi Lonkar, Ashling Holland, Brijesh Garg, Jeff Foy und James McArthur. „Design of a Phase 1, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-Ascending Doses of PGN-EDODM1 in Adult Participants with Myotonic Dystrophy Type 1 (DM1) (P6-8.004)“. In 2023 Annual Meeting Abstracts. Lippincott Williams & Wilkins, 2023. http://dx.doi.org/10.1212/wnl.0000000000203993.
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Pedrero Tejada, Sandra, Borja Ortiz De Urbina Antia, Idoia Salinas Garrido, Beatriz Gonzalez Quero, Sonia Castro Quintas, Amaia Urrutia Gajate, Lorea Martinez Indart, Valentin Cabriada Nuño und Pilar Marin Fernandez. „Assesment for Sleep in Myotonic Dystrophy type 1(MD-1) patients“. In ERS International Congress 2018 abstracts. European Respiratory Society, 2018. http://dx.doi.org/10.1183/13993003.congress-2018.pa2553.
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Durigan, Teodora Roballo, Marina Hideko Kinoshita Assahide und Leticia Sayuri Kinoshita Assahide. „Severe case of myotonic dystrophy type 1 associated with syringomyelia“. In SBN Conference 2022. Thieme Revinter Publicações Ltda., 2023. http://dx.doi.org/10.1055/s-0043-1774520.
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Miguel, Bernardo, und João Valente. „P009 Managing a trauma patient with myotonic dystrophy type-1“. In ESRA Abstracts, 41st Annual ESRA Congress, 4–7th September 2024, A201.1—A201. BMJ Publishing Group Ltd, 2024. http://dx.doi.org/10.1136/rapm-2024-esra.284.
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El-Wahsh, Shadi, Katrina Morris, Sandhya Limaye, Sean Riminton, Alastair Corbett und James Triplett. „4 Hypogammaglobulinemia and infection risk in myotonic dystrophy type 1“. In ANZAN Annual Scientific Meeting 2024 Abstracts, A2.2—A2. BMJ Publishing Group Ltd, 2024. http://dx.doi.org/10.1136/bmjno-2024-anzan.4.
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Gaeta, Roberta, Federica Di Giorgi, Miriam De Francesco, Mariapia Niceforo, Lorenzo Fontanelli, Alessandro Celi, Laura Carrozzi, Massimiliano Serradori und Marco Gherardi. „Correlation between limb muscle impairment and respiratory function in myotonic dystrophy type 1“. In ERS Congress 2024 abstracts, PA5278. European Respiratory Society, 2024. http://dx.doi.org/10.1183/13993003.congress-2024.pa5278.
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1
Kastreva, Kristina, und Ivailo Tournev. Clinical Data Analysis of the Bulgarian Patient Registry for Myotonic Dystrophy Type 1 and Type 2 – Part of the Global TREAT-NMD Registry. "Prof. Marin Drinov" Publishing House of Bulgarian Academy of Sciences, Juni 2020. http://dx.doi.org/10.7546/crabs.2020.06.18.
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