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Stem Cell Research Jun 2024Congenital myotonic dystrophy (CDM) is a genetic disease caused by an abnormally long CTG repeat expansion in the DMPK gene, which generally increases in size following...
Congenital myotonic dystrophy (CDM) is a genetic disease caused by an abnormally long CTG repeat expansion in the DMPK gene, which generally increases in size following intergenerational transmission. CDM is the rarest and most severe form of myotonic dystrophy type 1, yet an important number of patient-derived cells are needed to study this heterogeneous disease. Therefore, we have reprogrammed lymphoblastoid cells derived from a 3-year-old male with CDM into induced pluripotent stem cells (iPSCs; CBRCULi015-A) featuring 1800 CTG repeats and characterized their pluripotent state. This cell line constitutes an important resource to study CDM and potential treatments in vitro.
Topics: Humans; Myotonic Dystrophy; Induced Pluripotent Stem Cells; Male; Child, Preschool; Cell Line; Cell Differentiation; Myotonin-Protein Kinase
PubMed: 38704930
DOI: 10.1016/j.scr.2024.103430 -
BMC Psychology Apr 2024The COVID-19 pandemic substantially affected the lives of persons with inherited neuromuscular disorders (INMD), causing disruption in clinical and support services....
BACKGROUND
The COVID-19 pandemic substantially affected the lives of persons with inherited neuromuscular disorders (INMD), causing disruption in clinical and support services. While several studies have investigated mental health, distress and psychosocial resources in the general population during the pandemic, little is known about the experience of persons with INMD.
METHODS
This study was aimed to fill this gap by jointly investigating both psychopathological symptoms and psychosocial resources - specifically, resilience and perceived social support - among persons with INMD during the pandemic, taking into account demographic and clinical factors. Between April and December 2020, 59 participants with INMD (aged 15-59, 71.2% M) completed a questionnaire collecting demographic and clinical data, the Multidimensional Scale of Perceived Social Support, the Resilience Scale for Adults, and the Achenbach System of Empirically Based Assessment.
RESULTS
Overall, participants showed good levels of resilience and perceived social support. A minority of participants reported clinically relevant psychopathological symptoms, 28.81% for anxiety and depression. Most psychopathological symptoms were negatively correlated with resilience (-0.347 < r < - .420), but not significantly associated with social support. Consistent with previous studies, regression analyses highlighted that participants with Duchenne muscular dystrophy were more prone to report anxious and depressive symptoms (B = 1.748, p = .028, OR = 5.744), and participants with myotonic dystrophy, attention problems (B = 2.339, p = .006, OR = 10.376). Resilience emerged as a potential predictor of lower anxious-depressive symptoms (B=-1.264, p = .012, OR = 0.283).
CONCLUSIONS
The findings suggest the importance to investigate psychosocial resources in addition to psychopathology among persons with INMD, and to design interventions supporting resilience as a protective factor for mental health promotion.
Topics: Humans; COVID-19; Adult; Male; Female; Middle Aged; Resilience, Psychological; Neuromuscular Diseases; Social Support; Adolescent; Young Adult; Anxiety; Depression; Surveys and Questionnaires; SARS-CoV-2
PubMed: 38685111
DOI: 10.1186/s40359-024-01742-5 -
Revista de Neurologia May 2024Genetic myopathies constitute a collection of rare diseases that significantly impact patient functionality and quality of life. Early diagnosis of genetic myopathies... (Observational Study)
Observational Study
INTRODUCTION
Genetic myopathies constitute a collection of rare diseases that significantly impact patient functionality and quality of life. Early diagnosis of genetic myopathies can prevent future complications and provide families with genetic counselling. Despite the substantial impact of genetic myopathies on the adult population, the global epidemiology of these disorders is inadequately addressed in the literature.
AIMS
To enhance understanding of both the epidemiology and genetics of these disorders within the province of Alicante, situated in southeastern Spain.
MATERIAL AND METHODS
Between 2020 and 2022, a prospective observational study was conducted at the Alicante Health Area-General Hospital, enrolling patients aged 16 years or older with suspected genetic myopathies. Sociodemographic, clinical, and genetic data were collected. The reference date for prevalence calculation was established as December 31, 2022. Official demographic data of the health area were used to set the population at risk.
RESULTS
In total, 83 patients were identified with confirmed genetically related myopathy, resulting in an overall prevalence of 29.59 cases per 100,000 inhabitants. The diagnostic yield for molecular genetic testing was found to be 69.16%. The most prevalent genetic myopathies identified included myotonic dystrophy (27.5%), dystrophinopathies (15.7%), and facioscapulohumeral dystrophy (15.7%).
CONCLUSION
The prevalence of GMs can vary considerably depending on the geographical region and the studied population. The analysis of diagnostic yield suggests that genetic studies should be considered useful in the diagnosis of genetic myopathies.
Topics: Humans; Spain; Male; Female; Adult; Prospective Studies; Middle Aged; Prevalence; Muscular Diseases; Aged; Young Adult; Adolescent
PubMed: 38682761
DOI: 10.33588/rn.7809.2024071 -
Nigerian Journal of Clinical Practice Apr 2024Myotonic dystrophy (DM) is an autosomal dominant genetic disorder characterized by progressively worsening loss of muscle mass and weakness. Anesthesiologists face...
Myotonic dystrophy (DM) is an autosomal dominant genetic disorder characterized by progressively worsening loss of muscle mass and weakness. Anesthesiologists face challenges in managing these patients due to risks such as prolonged intubation and delayed recovery associated with anesthesia in such conditions. We report a case of a 40-year-old male patient undergoing open total gastrectomy under general anesthesia. After the surgery, we administered sugammadex to reverse neuromuscular blockade and confirmed the patient's spontaneous breathing. We then proceeded to extubate the patient. However, the patient experienced complications such as apnea, desaturation, and mental changes. The patient was re-intubated and transferred to the intensive care unit for ventilator support. He was diagnosed with DM by genetic test later. Poor preoperative assessment or undiagnosed DM in surgical patients can lead to severe complications. Thus, it is important to carefully check preoperative laboratory results, patient history, and physical findings.
Topics: Humans; Myotonic Dystrophy; Male; Adult; Anesthesia, General; Gastrectomy; Sugammadex; Neuromuscular Blockade
PubMed: 38679780
DOI: 10.4103/njcp.njcp_553_23 -
Archives of Cardiovascular Diseases 2024In France, mexiletine - a class I antiarrhythmic drug - can be prescribed for the symptomatic treatment of myotonia of the skeletal muscles in adult patients with... (Review)
Review
In France, mexiletine - a class I antiarrhythmic drug - can be prescribed for the symptomatic treatment of myotonia of the skeletal muscles in adult patients with myotonic dystrophy under a compassionate use programme. Mexiletine is used according to its summary of product characteristics, which describes its use for myotonia treatment in adult patients with non-dystrophic myotonia, a different neuromuscular condition without cardiac involvement. A cardiac assessment is required prior to initiation and throughout treatment due to potential proarrhythmic effects. The presence of conduction system disease, the most common cardiac manifestation of myotonic dystrophy, mandates repeated cardiac evaluations in patients with this condition, and becomes even more important when they are given mexiletine. A group of experts, including three neurologists and five cardiologists from French neuromuscular reference centres, were involved in a task force to develop a treatment algorithm to guide mexiletine use in myotonic dystrophy. The recommendations are based on data from a literature review of the safety of mexiletine-treated patients with myotonic dystrophy, the compassionate use protocol for mexiletine and the personal clinical experience of the experts. The main conclusion of the expert group is that, although existing safety data in mexiletine-treated patients with myotonic dystrophy are reassuring, cardiac assessments should be reinforced in such patients compared with mexiletine-treated patients with non-dystrophic myotonia. This expert opinion to guide mexiletine treatment in patients with myotonic dystrophy should help to reduce the risk of severe adverse events and facilitate interactions between specialists involved in the routine care of patients with myotonic dystrophy.
Topics: Adult; Humans; Algorithms; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Clinical Decision-Making; Compassionate Use Trials; Consensus; France; Mexiletine; Myotonic Dystrophy; Risk Assessment; Risk Factors; Treatment Outcome; Voltage-Gated Sodium Channel Blockers
PubMed: 38677940
DOI: 10.1016/j.acvd.2024.03.001 -
Tidsskrift For Den Norske Laegeforening... Apr 2024Myotonic dystrophy type 1 is an autosomal dominant, inherited multiorgan disorder that can affect people of all ages. It is the most prevalent inherited muscular disease... (Review)
Review
Myotonic dystrophy type 1 is an autosomal dominant, inherited multiorgan disorder that can affect people of all ages. It is the most prevalent inherited muscular disease in adults. Late diagnosis points to limited knowledge among the medical community that symptoms other than typical muscular symptoms can dominate. The condition often worsens with each generation and some families are severely affected. Significantly delayed diagnosis means a risk of more serious development of the disorder and inadequate symptomatic treatment. We hope that this clinical review article may lead to more rapid diagnosis and better follow-up of this patient group.
Topics: Myotonic Dystrophy; Humans; Delayed Diagnosis; Adult
PubMed: 38651711
DOI: 10.4045/tidsskr.23.0687 -
Biomedica : Revista Del Instituto... Mar 2024Introduction. During the development of the SARS-CoV-2 pandemic in Antioquia, we experienced epidemiological peaks related to the α, ɣ, β, ƛ, and δ variants. δ had...
Introduction. During the development of the SARS-CoV-2 pandemic in Antioquia, we experienced epidemiological peaks related to the α, ɣ, β, ƛ, and δ variants. δ had the highest incidence and prevalence. This lineage is of concern due to its clinical manifestations and epidemiological characteristics. A total of 253 δ sublineages have been reported in the PANGOLIN database. The sublineage identification through genomic analysis has made it possible to trace their evolution and propagation. Objective. To characterize the genetic diversity of the different SARS-CoV-2 δ sublineages in Antioquia and to describe its prevalence. Materials and methods. We collected sociodemographic information from 2,675 samples, and obtained 1,115 genomes from the GISAID database between July 12th, 2021, and January 18th, 2022. From the analyzed genomes, 515 were selected because of their high coverage values (>90%) to perform phylogenetic analysis and to infer allele frequencies of mutations of interest. Results. We characterized 24 sublineages. The most prevalent was AY.25. Mutations of interest as L452R, P681R, and P681H were identified in this sublineage, comprising a frequency close to 0.99. Conclusions. This study identified that the AY.25 sublineage has a transmission advantage compared to the other δ sublineages. This attribute may be related to the presence of the L452R and P681R mutations associated in other studies with higher evasion of the immune system and less efficacy of drugs against SARS-CoV-2.
Topics: Colombia; COVID-19; Humans; SARS-CoV-2; Phylogeny; Genome, Viral; Male; Female; Mutation; Adult; Middle Aged; Pandemics; Young Adult; Aged; Adolescent; Gene Frequency; Genetic Variation
PubMed: 38648352
DOI: 10.7705/biomedica.6862 -
International Journal of Cardiology Jul 2024Cardiac involvement represents a major cause of morbidity and mortality in patients with myotonic dystrophy type 1 (DM1) and prevention of sudden cardiac death (SCD) is...
BACKGROUND
Cardiac involvement represents a major cause of morbidity and mortality in patients with myotonic dystrophy type 1 (DM1) and prevention of sudden cardiac death (SCD) is a central part of patient care. We investigated the natural history of cardiac involvement in patients with DM1 to provide an evidence-based foundation for adjustment of follow-up protocols.
METHODS
Patients with genetically confirmed DM1 were identified. Data on patient characteristics, performed investigations (12 lead ECG, Holter monitoring and echocardiography), and clinical outcomes were retrospectively collected from electronic health records.
RESULTS
We included 195 patients (52% men) with a mean age at baseline evaluation of 41 years (range 14-79). The overall prevalence of cardiac involvement increased from 42% to 66% after a median follow-up of 10.5 years. There was a male predominance for cardiac involvement at end of follow-up (74 vs. 44%, p < 0.001). The most common types of cardiac involvement were conduction abnormalities (48%), arrhythmias (35%), and left ventricular systolic dysfunction (21%). Only 17% of patients reported cardiac symptoms. The standard 12‑lead ECG was the most sensitive diagnostic modality and documented cardiac involvement in 24% at baseline and in 49% at latest follow-up. However, addition of Holter monitoring and echocardiography significantly increased the diagnostic yield with 18 and 13% points at baseline and latest follow-up, respectively. Despite surveillance 35 patients (18%) died during follow-up; seven due to SCD.
CONCLUSIONS
In patients with DM1 cardiac involvement was highly prevalent and developed during follow-up. These findings justify lifelong follow-up with ECG, Holter, and echocardiography.
CLINICAL PERSPECTIVE
What is new? What are the clinical implications?
Topics: Humans; Myotonic Dystrophy; Male; Female; Adult; Middle Aged; Follow-Up Studies; Young Adult; Retrospective Studies; Adolescent; Aged; Electrocardiography, Ambulatory; Echocardiography; Heart Diseases; Electrocardiography
PubMed: 38643802
DOI: 10.1016/j.ijcard.2024.132070 -
Frontiers in Cellular Neuroscience 2024Myotonic dystrophy (DM) encompasses a spectrum of neuromuscular diseases characterized by myotonia, muscle weakness, and wasting. Recent research has led to the... (Review)
Review
Myotonic dystrophy (DM) encompasses a spectrum of neuromuscular diseases characterized by myotonia, muscle weakness, and wasting. Recent research has led to the recognition of DM as a neurological disorder. Cognitive impairment is a central nervous system condition that has been observed in various forms of DM. Neuroimaging studies have increasingly linked DM to alterations in white matter (WM) integrity and highlighted the relationship between cognitive impairment and abnormalities in WM structure. This review aims to summarize investigations into cognitive impairment and brain abnormalities in individuals with DM and to elucidate the correlation between these factors and the potential underlying mechanisms contributing to these abnormalities.
PubMed: 38638300
DOI: 10.3389/fncel.2024.1369332 -
Nature Communications Apr 2024Epigenetic defects caused by hereditary or de novo mutations are implicated in various human diseases. It remains uncertain whether correcting the underlying mutation...
Epigenetic defects caused by hereditary or de novo mutations are implicated in various human diseases. It remains uncertain whether correcting the underlying mutation can reverse these defects in patient cells. Here we show by the analysis of myotonic dystrophy type 1 (DM1)-related locus that in mutant human embryonic stem cells (hESCs), DNA methylation and H3K9me3 enrichments are completely abolished by repeat excision (CTG2000 expansion), whereas in patient myoblasts (CTG2600 expansion), repeat deletion fails to do so. This distinction between undifferentiated and differentiated cells arises during cell differentiation, and can be reversed by reprogramming of gene-edited myoblasts. We demonstrate that abnormal methylation in DM1 is distinctively maintained in the undifferentiated state by the activity of the de novo DNMTs (DNMT3b in tandem with DNMT3a). Overall, the findings highlight a crucial difference in heterochromatin maintenance between undifferentiated (sequence-dependent) and differentiated (sequence-independent) cells, thus underscoring the role of differentiation as a locking mechanism for repressive epigenetic modifications at the DM1 locus.
Topics: Humans; Myotonic Dystrophy; Heterochromatin; Cell Differentiation; DNA Methylation; Epigenesis, Genetic
PubMed: 38627364
DOI: 10.1038/s41467-024-47217-4