المؤلفون: Zhong, Huahua¹ (AUTHOR), Zeng, Li² (AUTHOR), Yu, Xuefan³ (AUTHOR), Ke, Qing⁴ (AUTHOR), Dong, Jihong⁵ (AUTHOR), Chen, Yan⁶ (AUTHOR), Luo, Lijun⁷ (AUTHOR), Chang, Xueli⁸ (AUTHOR), Guo, Junhong⁸ (AUTHOR), Wang, Yiqi⁹ (AUTHOR), Xiong, Hui¹⁰ (AUTHOR), Liu, Rongrong¹¹ (AUTHOR), Liu, Changxia¹² (AUTHOR), Wu, Jibao¹³ (AUTHOR), Lin, Jie¹ (AUTHOR), Xi, Jianying¹ (AUTHOR), Zhu, Wenhua¹ (AUTHOR), Tan, Song² (AUTHOR), Liu, Fuchen¹⁴ (AUTHOR), Lu, Jiahong¹ (AUTHOR)

المصدر: Orphanet Journal of Rare Diseases. 3/7/2024, Vol. 19 Issue 1, p1-9. 9p.

مصطلحات موضوعية: *MYOTONIA atrophica, *DROWSINESS, *FACIOSCAPULOHUMERAL muscular dystrophy, *NEUROMUSCULAR diseases, *MUSCULAR dystrophy, *MUSCLE weakness, *EPWORTH Sleepiness Scale

مستخلص: Background: As the most common subtype of adult muscular dystrophy worldwide, large cohort reports on myotonic dystrophy type I (DM1) in China are still lacking. This study aims to analyze the genetic and clinical characteristics of Chinese Han DM1 patients. Methods: Based on the multicenter collaborating effort of the Pan-Yangtze River Delta Alliance for Neuromuscular Disorders, patients with suspected clinical diagnoses of DM1 were genetically confirmed from January 2020 to April 2023. Peak CTG repeats in the DMPK gene were analyzed using triplet repeat-primed PCR (TP-PCR) and flanking PCR. Time-to-event analysis of onset age in females and males was performed. Additionally, detailed clinical features and longitudinal changes from the disease onset in 64 DM1 patients were retrospectively collected and analyzed. The Epworth Sleepiness Scale and Fatigue Severity Scale were used to quantify the severity of daytime sleepiness and fatigue. Results: Among the 211 genetically confirmed DM1 patients, the mean age at diagnosis was 40.9 ± 12.2 (range: 12–74) with a male-to-female ratio of 124:87. The average size of CTG repeats was 511.3 (range: 92–1945). Among the DM1 patients with comprehensive clinical data (n = 64, mean age 41.0 ± 12.0), the age at onset was significantly earlier in males than in females (4.8 years earlier, p = 0.026). Muscle weakness (92.2%), myotonia (85.9%), and fatigue (73.4%) were the most prevalent clinical features. The predominant involved muscles at onset are hands (weakness or myotonia) (52.6%) and legs (walking disability) (42.1%). Of them, 70.3% of patients had daytime sleepiness, 14.1% had cataract surgery, 7.8% used wheelchairs, 4.7% required ventilatory support, and 1.6% required gastric tubes. Regarding the comorbidities, 4.7% of patients had tumors, 17.2% had diabetes, 23.4% had dyspnea, 28.1% had intermittent insomnia, 43.8% experienced dysphagia, and 25% exhibited cognitive impairment. Chinese patients exhibited smaller size of CTG repeats (468 ± 139) than those reported in Italy (613 ± 623), the US (629 ± 386), and Japan (625 [302, 1047]), and milder phenotypes with less multisystem involvement. Conclusion: The Chinese Han DM1 patients presented milder phenotypes compared to their Caucasian and Japanese counterparts. A male predominance and an early age of onset were identified in male Chinese Han DM1 patients. [ABSTRACT FROM AUTHOR]

المؤلفون: Nakamori, Masayuki¹ (AUTHOR) mnakamor@neurol.med.osaka‐u.ac.jp

المصدر: Neurology & Clinical Neuroscience. Jan2024, Vol. 12 Issue 1, p16-23. 8p.

مصطلحات موضوعية: *MYOTONIA atrophica, *SPINOCEREBELLAR ataxia, *ALTERNATIVE RNA splicing, *MUSCULAR dystrophy, *MYOCARDIUM, *TANDEM repeats

مستخلص: Myotonic dystrophy (DM) is the most common muscular dystrophy in adults, affecting skeletal muscle as well as cardiac and smooth muscle. Furthermore, involvement of the central nervous system, endocrine organs, and eyes is often seen, with debilitating consequences. The condition is an autosomal‐dominant inherited genetic disease caused by abnormal genomic expansion of tandem repeats. Myotonic dystrophy type 1 (DM1) results from expansion of a CTG repeat in the 3′‐untranslated region of the gene encoding dystrophia myotonica‐protein kinase (DMPK), whereas myotonic dystrophy type 2 (DM2) is caused by expansion of a CCTG repeat in the first intron of the gene encoding CCHC‐type zinc finger nucleic acid‐binding protein (CNBP). Both types of DM exhibit abnormal mRNA transcribed from the mutated gene containing expanded repeats, which exert toxic gain‐of‐function effects on various proteins involved in cellular processes such as alternative splicing, signaling pathways, and cellular senescence. The present review discusses the expanded‐repeat‐RNA‐mediated molecular pathomechanisms in DM. [ABSTRACT FROM AUTHOR]

المؤلفون: Marzullo, Marta¹ (AUTHOR) marta.marzullo@uniroma1.it, Coni, Sonia² (AUTHOR), De Simone, Assia¹ (AUTHOR), Canettieri, Gianluca^2,3 (AUTHOR), Ciapponi, Laura¹ (AUTHOR) laura.ciapponi@uniroma1.it

المصدر: International Journal of Molecular Sciences. Sep2023, Vol. 24 Issue 18, p14182. 13p.

مصطلحات موضوعية: *DROSOPHILA melanogaster, *MYOTONIA atrophica, *MUSCULAR dystrophy, *GENETIC disorders, *SKELETAL muscle, *DROSOPHILA, *ZINC-finger proteins

مستخلص: Myotonic dystrophy 2 (DM2) is a genetic multi-systemic disease primarily affecting skeletal muscle. It is caused by CCTGn expansion in intron 1 of the CNBP gene, which encodes a zinc finger protein. DM2 disease has been successfully modeled in Drosophila melanogaster, allowing the identification and validation of new pathogenic mechanisms and potential therapeutic strategies. Here, we describe the principal tools used in Drosophila to study and dissect molecular pathways related to muscular dystrophies and summarize the main findings in DM2 pathogenesis based on DM2 Drosophila models. We also illustrate how Drosophila may be successfully used to generate a tractable animal model to identify novel genes able to affect and/or modify the pathogenic pathway and to discover new potential drugs. [ABSTRACT FROM AUTHOR]

المؤلفون: Li, Mao, Li, Yifan, Wang, Zhanjun, Cui, Fang, Yang, Fei, Wang, Hongfen, Shi, Qiang, Huang, Xusheng

المصدر: Neurological Research; Jul2024, Vol. 46 Issue 7, p613-625, 13p

مصطلحات موضوعية: GENE expression, MYOTONIA atrophica, SKELETAL muscle, RNA splicing, FACIOSCAPULOHUMERAL muscular dystrophy, MUSCULAR dystrophy

مستخلص: Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults, yet there are currently no disease-modifying treatments. Disrupted miRNA expressions may lead to dysregulation of target mRNAs and dysfunction involved in DM1 pathogenic mechanism. We used microarray platforms to examine the miRNA/mRNA expression profiles in skeletal muscle biopsies derived from DM1 patients and matched controls. Bioinformatics analysis and dual-luciferase reporter assay were conducted to provide insight into miRNA-mRNA regulatory networks altered in DM1. Twenty-three differentially expressed miRNAs and 135 differentially expressed genes were identified. qPCR confirmed that miR-3201, myogenic factor 5 (MYF5), myogenic differentiation 1 (MYOD1), CUGBP, Elav-like family member 1 (CELF1), and CELF2 were significantly up-regulated, while miR-196a, miR-200c, and miR-146a were significantly down-regulated. Enriched functions and pathways such as multicellular organismal development, RNA splicing, cell differentiation, and spliceosome are relevant to DM1. The miRNA-mRNA interaction network revealed that miR-182, miR-30c-2, and miR-200c were the critical nodes that potentially interacted with hub genes. Luciferase reporter assay confirmed the direct interaction between miR-196a and CELF2. Those results implied that the observed miRNA/mRNA dysregulation could contribute to specific functions and pathways related to DM1 pathogenesis, highlighting the dysfunction of miR-196a and CELF2. [ABSTRACT FROM AUTHOR]

: Copyright of Neurological Research is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Ilic Zivojinovic, Jelena¹ (AUTHOR), Djurdjevic, Katarina¹ (AUTHOR), Bozovic, Ivo² (AUTHOR), Meola, Giovanni³ (AUTHOR), Peric, Marina⁴ (AUTHOR), Azanjac Arsic, Ana⁵ (AUTHOR), Basta, Ivana² (AUTHOR), Rakocevic-Stojanovic, Vidosava² (AUTHOR), Peric, Stojan^2,6 (AUTHOR) stojanperic@gmail.com

المصدر: Neurological Sciences. Jul2023, Vol. 44 Issue 7, p2231-2237. 7p. 1 Diagram, 3 Charts.

مصطلحات موضوعية: *COVID-19 pandemic, *MYOTONIA atrophica, *COVID-19, *MUSCULAR dystrophy, *COVID-19 vaccines

مستخلص: Introduction: Myotonic dystrophy type 1 (DM1) is the most prevalent muscular dystrophy in adults. People with DM1 might represent a high-risk population for respiratory infections, including COVID-19. Our aim was to evaluate the characteristics of COVID-19 infection and vaccination rate in DM1 patients. Methods: This cross-sectional cohort study included 89 patients from the Serbian registry for myotonic dystrophies. Mean age at testing was 48.4 ± 10.4 years with 41 (46.1%) male patients. Mean duration of the disease was 24.0 ± 10.3 years. Results: COVID-19 infection was reported by 36 (40.4%) DM1 patients. Around 14% of patients had a more severe form of COVID-19 requiring hospitalization. The severity of COVID-19 was in accordance with the duration of DM1. A severe form of COVID-19 was reported in 20.8% of patients who were not vaccinated against SARS-CoV-2 and in none of the vaccinated ones. The majority of 89 tested patients (66.3%) were vaccinated against SARS-CoV-2. About half of them (54.2%) received three doses and 35.6% two doses of vaccine. Mild adverse events after vaccination were recorded in 20.3% of patients. Conclusions: The percentage of DM1 patients who suffered from COVID-19 was like in general population, but with more severe forms in DM1, especially in patients with longer DM1 duration. The study indicated an overall favorable safety profile of COVID-19 vaccines among individuals with DM1 and its ability to protect them from severe COVID-19. [ABSTRACT FROM AUTHOR]

المؤلفون: D'Ambrosio, Eleonora S.¹ (AUTHOR), Gonzalez-Perez, Paloma² (AUTHOR) pgonzalezperez@partners.org

المصدر: Journal of Clinical Medicine. Mar2023, Vol. 12 Issue 5, p1939. 14p.

مصطلحات موضوعية: *MYOTONIA atrophica, *SPINOCEREBELLAR ataxia, *PATIENT compliance, *MUSCULAR dystrophy, *EARLY detection of cancer, *MEDICAL screening

مستخلص: Myotonic dystrophy (DM) is the most common muscular dystrophy in adults. Dominantly inherited CTG and CCTG repeat expansions in DMPK and CNBP genes cause DM type 1 (DM1) and 2 (DM2), respectively. These genetic defects lead to the abnormal splicing of different mRNA transcripts, which are thought to be responsible for the multiorgan involvement of these diseases. In ours and others' experience, cancer frequency in patients with DM appears to be higher than in the general population or non-DM muscular dystrophy cohorts. There are no specific guidelines regarding malignancy screening in these patients, and the general consensus is that they should undergo the same cancer screening as the general population. Here, we review the main studies that investigated cancer risk (and cancer type) in DM cohorts and those that researched potential molecular mechanisms accounting for DM carcinogenesis. We propose some evaluations to be considered as malignancy screening in patients with DM, and we discuss DM susceptibility to general anesthesia and sedatives, which are often needed for the management of cancer. This review underscores the importance of monitoring the adherence of patients with DM to malignancy screenings and the need to design studies that determine whether they would benefit from a more intensified cancer screening than the general population. [ABSTRACT FROM AUTHOR]

المؤلفون: Stoodley, Jessica^1,2 (AUTHOR), Vallejo-Bedia, Francisco^1,2 (AUTHOR), Seone-Miraz, David^1,2 (AUTHOR), Debasa-Mouce, Manuel^1,2 (AUTHOR), Wood, Matthew J. A.^1,2 (AUTHOR), Varela, Miguel A.^1,2 (AUTHOR) miguel.varela@paediatrics.ox.ac.uk

المصدر: International Journal of Molecular Sciences. Feb2023, Vol. 24 Issue 3, p2697. 13p.

مصطلحات موضوعية: *MYOTONIA atrophica, *MUSCULAR dystrophy, *MOLECULAR pathology, *MYOCARDIUM, *FACIOSCAPULOHUMERAL muscular dystrophy, *DYSTROPHY, *BINDING sites

مستخلص: Myotonic dystrophy type 1 (DM1) is one of the most common muscular dystrophies and can be potentially treated with antisense therapy decreasing mutant DMPK, targeting miRNAs or their binding sites or via a blocking mechanism for MBNL1 displacement from the repeats. Unconjugated antisense molecules are able to correct the disease phenotype in mouse models, but they show poor muscle penetration upon systemic delivery in DM1 patients. In order to overcome this challenge, research has focused on the improvement of the therapeutic window and biodistribution of antisense therapy using bioconjugation to lipids, cell penetrating peptides or antibodies. Antisense conjugates are able to induce the long-lasting correction of DM1 pathology at both molecular and functional levels and also efficiently penetrate hard-to-reach tissues such as cardiac muscle. Delivery to the CNS at clinically relevant levels remains challenging and the use of alternative administration routes may be necessary to ameliorate some of the symptoms experienced by DM1 patients. With several antisense therapies currently in clinical trials, the outlook for achieving a clinically approved treatment for patients has never looked more promising. [ABSTRACT FROM AUTHOR]

المؤلفون: Rossi, Salvatore¹ (AUTHOR), Silvestri, Gabriella^1,2 (AUTHOR) gabriella.silvestri@unicatt.it

المصدر: International Journal of Molecular Sciences. Feb2023, Vol. 24 Issue 3, p2204. 10p.

مصطلحات موضوعية: *CENTRAL nervous system, *MYOTONIA atrophica, *TRINUCLEOTIDE repeats, *FACIOSCAPULOHUMERAL muscular dystrophy, *MUSCULAR dystrophy, *TAU proteins

مستخلص: Myotonic dystrophy type 1 (DM1), commonly known as Steinert's disease (OMIM #160900), is the most common muscular dystrophy among adults, caused by an unstable expansion of a CTG trinucleotide repeat in the 3′ untranslated region (UTR) of DMPK. Besides skeletal muscle, central nervous system (CNS) involvement is one of the core manifestations of DM1, whose relevant cognitive, behavioral, and affective symptoms deeply affect quality of life of DM1 patients, and that, together with muscle and heart, may profoundly influence the global disease burden and overall prognosis. Therefore, CNS should be also included among the main targets for future therapeutic developments in DM1, and, in this regard, identifying a cost-effective, easily accessible, and sensitive diagnostic and monitoring biomarker of CNS involvement in DM1 represents a relevant issue to be addressed. In this mini review, we will discuss all the papers so far published exploring the usefulness of both cerebrospinal fluid (CSF) and blood-based biomarkers of CNS involvement in DM1. Globally, the results of these studies are quite consistent on the value of CSF and blood Neurofilament Light Chain (NfL) as a biomarker of CNS involvement, with less robust results regarding levels of tau protein or amyloid-beta. [ABSTRACT FROM AUTHOR]

المؤلفون: Izzo, Mariapaola¹ (AUTHOR) mariapaola.izzo@ibbc.cnr.it, Battistini, Jonathan¹ (AUTHOR) jonathan.battistini@ibbc.cnr.it, Provenzano, Claudia¹ (AUTHOR) claudia.provenzano@cnr.it, Martelli, Fabio² (AUTHOR) fabio.martelli@grupposandonato.it, Cardinali, Beatrice¹ (AUTHOR) beatrice.cardinali@cnr.it, Falcone, Germana¹ (AUTHOR) beatrice.cardinali@cnr.it

المصدر: International Journal of Molecular Sciences. May2022, Vol. 23 Issue 9, p4622-4622. 25p.

مصطلحات موضوعية: *MYOTONIA atrophica, *GENOME editing, *FACIOSCAPULOHUMERAL muscular dystrophy, *MUSCULAR dystrophy, *CENTRAL nervous system, *MYOCARDIUM

مستخلص: Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy affecting many different body tissues, predominantly skeletal and cardiac muscles and the central nervous system. The expansion of CTG repeats in the DM1 protein-kinase (DMPK) gene is the genetic cause of the disease. The pathogenetic mechanisms are mainly mediated by the production of a toxic expanded CUG transcript from the DMPK gene. With the availability of new knowledge, disease models, and technical tools, much progress has been made in the discovery of altered pathways and in the potential of therapeutic intervention, making the path to the clinic a closer reality. In this review, we describe and discuss the molecular therapeutic strategies for DM1, which are designed to directly target the CTG genomic tract, the expanded CUG transcript or downstream signaling molecules. [ABSTRACT FROM AUTHOR]

المؤلفون: Unni, Jiji, Daryani, Deepak, Uthkal, M, Mustafa, Shabil

المصدر: International Journal of Applied & Basic Medical Research; Oct-Dec2023, Vol. 13 Issue 4, p255-258, 4p

مصطلحات موضوعية: ODONTOGENIC tumors, DYSTROPHY, MYOTONIA atrophica, MUSCLE weakness, MUSCULAR dystrophy, ADENOMATOID tumors, ARACHNOID cysts

مستخلص: Myotonic dystrophy, also referred myotonic muscular dystrophy, is an autosomal dominant, slowly progressive, multisystem disease characterized by skeletal muscle weakness, wasting, and myotonia. A hybrid tumor of odontogenic apparatus is a lesion showing combined histopathological characteristics of two or more previously recognized odontogenic tumors and/or cysts of different categories. We, therefore, report a case of hybrid tumor (adenomatoid odontogenic tumor associated with calcifying cystic odontogenic tumor) in a myotonic dystrophic patient. [ABSTRACT FROM AUTHOR]

: Copyright of International Journal of Applied & Basic Medical Research is the property of Wolters Kluwer India Pvt Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)