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Methods in Molecular Biology (Clifton,... 2021Fibrosis in skeletal muscle is the natural tissue response to persistent damage and chronic inflammatory states, cursing with altered muscle stem cell regenerative...
Fibrosis in skeletal muscle is the natural tissue response to persistent damage and chronic inflammatory states, cursing with altered muscle stem cell regenerative functions and increased activation of fibrogenic mesenchymal stromal cells. Exacerbated deposition of extracellular matrix components is a characteristic feature of human muscular dystrophies, neurodegenerative diseases affecting muscle and aging. The presence of fibrotic tissue not only impedes normal muscle contractile functions but also hampers effective gene and cell therapies. There is a lack of appropriate experimental models to study fibrosis. In this chapter, we highlight recent developments on skeletal muscle fibrosis in mice and expand previously described methods by our group to exacerbate and accelerate fibrosis development in murine muscular dystrophy models and to study the presence of fibrosis in muscle samples. These methods will help understand the molecular and biological mechanisms involved in muscle fibrosis and to identify novel therapeutic strategies to limit the progression of fibrosis in muscular dystrophy.
Topics: Animals; Disease Models, Animal; Extracellular Matrix; Fibrosis; Humans; Male; Mice; Mice, Inbred mdx; Muscle, Skeletal; Muscular Dystrophies; Signal Transduction
PubMed: 34028754
DOI: 10.1007/978-1-0716-1382-5_24 -
International Heart Journal Jan 2019Emery-Dreifuss muscular dystrophy (EDMD) is a group of hereditary muscular dystrophy syndrome caused by deficiency of genes encoding nuclear envelope proteins. Patients... (Review)
Review
Emery-Dreifuss muscular dystrophy (EDMD) is a group of hereditary muscular dystrophy syndrome caused by deficiency of genes encoding nuclear envelope proteins. Patients having EDMD show the triad of muscle dystrophy, joint contracture, and cardiac disease. In almost all patients, cardiac involvement is prevalent and is the most severe aspect of EDMD. Cardiac disease is predominantly shown by conduction defects, atrial fibrillation/flutter, and atrial standstill. Sudden death and heart failure because of left ventricular dysfunction are important causes of mortality, particularly in those patients that have the LMNA mutation. Medical treatment of EDMD is limited to addressing symptoms and ambulation support; moreover, pacemaker implantation is necessary when there are severe conduction defects and bradycardia occurs. Note that automated defibrillation devices may be considered for those patients who have a high risk of sudden death, rate, or rhythm control. Also, anticoagulation should be initiated in those patients who have atrial fibrillation/flutter. Thus, for optimal management, a multidisciplinary approach is required.
Topics: Abnormalities, Multiple; Anticoagulants; Atrial Fibrillation; Cardiomyopathies; Cleft Palate; Contracture; Death, Sudden; Female; Genetic Diseases, Inborn; Heart Atria; Heart Block; Heart Diseases; Humans; Hydrocephalus; Interdisciplinary Communication; Limb Deformities, Congenital; Male; Muscular Dystrophies; Muscular Dystrophy, Emery-Dreifuss; Pacemaker, Artificial; Ventricular Dysfunction, Left
PubMed: 30518714
DOI: 10.1536/ihj.17-604 -
Chinese Medical Journal Nov 2017The aim was to update the genetic and clinical advances of congenital muscular dystrophy (CMD), based on a systematic review of the literature from 1991 to 2017. (Review)
Review
OBJECTIVE
The aim was to update the genetic and clinical advances of congenital muscular dystrophy (CMD), based on a systematic review of the literature from 1991 to 2017.
DATA SOURCES
Articles in English published in PubMed from 1991 to 2017 English were searched. The terms used in the literature searches were CMD.
STUDY SELECTION
The task force initially identified citations for 98 published articles. Of the 98 articles, 52 studies were selected after further detailed review. Three articles, which were not written in English, were excluded from the study. This study referred to all the important and English literature in full.
RESULTS
CMD is a group of early-onset disorders encompassing great clinical and genetic heterogeneity. Patients present with muscle weakness typically from birth to early infancy, delay or arrest of gross motor development, and joint and/or spinal rigidity. The diagnosis of CMD relies on clinical findings, brain and muscle imaging, muscle biopsy histology, muscle and/or skin immunohistochemical staining, and molecular genetic testing.
CONCLUSIONS
Advances in next-generation sequencing and histopathological techniques have enabled the recognition of distinct CMD subtypes supported by specific gene identification. Genetic counseling and multidisciplinary management of CMD play an important role in help patients and their family. Further elucidation of the significant clinical and genetic heterogeneity, therapeutic targets, and the clinical care for patients remains our challenge for the future.
Topics: High-Throughput Nucleotide Sequencing; Humans; Muscle, Skeletal; Muscular Dystrophies; Muscular Dystrophies, Limb-Girdle
PubMed: 29067961
DOI: 10.4103/0366-6999.217091 -
Fortschritte Der Neurologie-Psychiatrie Sep 2018Myotonic syndromes are rare neuromuscular diseases characterized by the clinical or neurophysiological detection of myotonia. The genetic defects involve primarily or... (Review)
Review
Myotonic syndromes are rare neuromuscular diseases characterized by the clinical or neurophysiological detection of myotonia. The genetic defects involve primarily or secondarily the muscular isoforms of the ion channels. The channel dysfunction consecutively leads to a hyper-excitability of the muscle membrane and the clinical symptom myotonia. Two forms of dystrophic myotonic diseases are currently known: the myotonic dystrophy type 1 (DM1) and the myotonic dystrophy type 2 (DM2). They are multisystemic diseases clinically characterized by a combination of myotonia and other muscular symptoms (muscle weakness, wasting and myalgia) together with the involvement of other organs and systems (cataract, diabetes, heart diseases, hormone dysfunctions). The non-dystrophic myotonic diseases are caused by mutations affecting either the chloride ion channels or the sodium ion channels. The clinical picture is dominated by the presence of myotonia and other minor muscular complaints as mild episodic weakness and muscle hypertrophy. The differential diagnosis among the myotonic syndromes is extremely challenging leading to a significant diagnostic delay. This review will update on the main clinical, diagnostic and therapeutic aspects of myotonic syndromes to guide general neurologists through an earlier diagnosis and better management.
Topics: Delayed Diagnosis; Humans; Muscular Dystrophies; Myotonia
PubMed: 30248690
DOI: 10.1055/a-0635-8285 -
Neuromuscular Disorders : NMD Jul 2018Skeletal muscle or cardiac symptoms are known to appear in a certain proportion of female patients carrying the dystrophin gene mutation. There is limited high-quality... (Review)
Review
Skeletal muscle or cardiac symptoms are known to appear in a certain proportion of female patients carrying the dystrophin gene mutation. There is limited high-quality evidence to guide the treatment of female carriers of Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD). The available evidence is mainly based on expert opinions and clinical experience. To improve this situation, we reviewed 1002 reports published from 1967 to 2017 to assess the following themes: epidemiology, clinical symptoms, cardiomyopathy, burdens on parents or caregivers, pregnancy or delivery, and prognosis. We aimed to provide guidance for the provision of support, care, and education for patients, caregivers, and health care professionals. There were 271 reports before 1987, and 731 reports after 1987 when dystrophin was first recognized. In this review, we mainly selected 37 papers that were reported after 1987. In seven large research papers, the incidence of skeletal muscle damage among female carriers, including asymptomatic carriers, was reported as 2.5%-19%, and the incidence of dilated cardiomyopathy was 7.3%-16.7% for DMD and 0%-13.3% for BMD. We integrated and summarized the genetically definite manifesting carriers with skeletal muscle symptoms from 10 case series. In combined data, among 93 manifesting carriers, 16 (17.2%) presented with cardiac abnormalities. The frequency of manifesting carriers complicated by cardiomyopathy increased with age. Reports on cardiac magnetic resonance in female carriers and the burden on caregivers are increasing, whereas literatures concerning pregnancy, delivery, and prognosis in female carriers are limited. This represents a future direction for research.
Topics: Cardiomyopathies; Dystrophin; Female; Heterozygote; Humans; Muscle, Skeletal; Muscular Dystrophies
PubMed: 29801751
DOI: 10.1016/j.nmd.2018.04.005 -
Clinics in Perinatology Mar 2020The congenital muscular dystrophies and congenital myopathies are a heterogenous group of diseases with a wide variety of presentations and outcomes. With the growing... (Review)
Review
The congenital muscular dystrophies and congenital myopathies are a heterogenous group of diseases with a wide variety of presentations and outcomes. With the growing understanding of genetic involvement, and developing therapies, having a genetically confirmed diagnosis with phenotype correlation is essential. To achieve this, a structured approach is warranted to each child to ensure that mimickers are excluded. By structuring the evaluation appropriately, the clinician can help expedite the evaluation of these infants in a cost-effective manner. Understanding the pitfalls of each step of testing will allow the clinician to better understand variants in presentation and avoid cognitive errors in the process.
Topics: Diagnosis, Differential; Humans; Infant, Newborn; Muscular Diseases; Muscular Dystrophies; Neonatal Screening; Phenotype
PubMed: 32000926
DOI: 10.1016/j.clp.2019.10.005 -
Methods in Molecular Biology (Clifton,... 2023Muscular dystrophies are a group of genetic disorders characterized by varying degrees of progressive muscle weakness and degeneration. They are clinically and... (Review)
Review
Muscular dystrophies are a group of genetic disorders characterized by varying degrees of progressive muscle weakness and degeneration. They are clinically and genetically heterogeneous but share the common histological features of dystrophic muscle. There is currently no cure for muscular dystrophies, which is of particular concern for the more disabling and/or lethal forms of the disease. Through the years, several therapies have encouragingly been developed for muscular dystrophies and include genetic, cellular, and pharmacological approaches. In this chapter, we undertake a comprehensive exploration of muscular dystrophy therapeutics under current development. Our review includes antisense therapy, CRISPR, gene replacement, cell therapy, nonsense suppression, and disease-modifying small molecule compounds.
Topics: Humans; Muscular Dystrophies; Genetic Therapy; Cell- and Tissue-Based Therapy
PubMed: 36401021
DOI: 10.1007/978-1-0716-2772-3_1 -
Indian Journal of Pathology &... May 2022Muscular dystrophies are a clinically and genetically heterogeneous group of disorders involving the skeletal muscles. They have a progressive clinical course and are... (Review)
Review
Muscular dystrophies are a clinically and genetically heterogeneous group of disorders involving the skeletal muscles. They have a progressive clinical course and are characterized by muscle fiber degeneration. Congenital muscular dystrophies (CMD) include dystroglycanopathies, merosin-deficient CMD, collagen VI-deficient CMD, SELENON-related rigid spine muscular dystrophy, and LMNA-related CMD. Childhood and adult-onset muscular dystrophies include dystrophinopathies, limb-girdle muscular dystrophies, Emery-Dreifuss muscular dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy. Traditionally, muscle biopsy and histopathology along with special pathology techniques such as immunohistochemistry or immunoblotting were used for the diagnosis of muscular dystrophies. However, recent advances in molecular genetic testing, especially the next-generation sequencing technology, have revolutionized the diagnosis of muscular dystrophies. Identification of the underlying genetic basis helps in appropriate management and prognostication of the affected individual and genetic counseling of the family. In addition, identification of the exact disease-causing mutations is necessary for accurate prenatal genetic testing and carrier testing, to prevent recurrence in the family. Mutation identification is also essential for initiating mutation-specific therapies (which have been developed recently, especially for Duchenne muscular dystrophy) and for enrolment of patients into ongoing therapeutic clinical trials. The 'genetic testing first' approach has now become the norm in most centers. Nonetheless, muscle biopsy-based testing still has an important role to play, especially for cases where genetic testing is negative or inconclusive for the etiology.
Topics: Adult; Child; Female; Genetic Testing; High-Throughput Nucleotide Sequencing; Humans; Muscle, Skeletal; Muscular Dystrophies; Mutation; Pregnancy
PubMed: 35562158
DOI: 10.4103/ijpm.ijpm_1074_21 -
Anesthesiology May 2021
Topics: Anesthesia; Child; Cysts; Humans; Muscular Dystrophies; Pierre Robin Syndrome; Sclerosis
PubMed: 33529318
DOI: 10.1097/ALN.0000000000003698 -
Journal of Neurology, Neurosurgery, and... Mar 2015Collagen VI is widely distributed throughout extracellular matrices (ECMs) in various tissues. In skeletal muscle, collagen VI is particularly concentrated in and... (Review)
Review
Collagen VI is widely distributed throughout extracellular matrices (ECMs) in various tissues. In skeletal muscle, collagen VI is particularly concentrated in and adjacent to basement membranes of myofibers. Ullrich congenital muscular dystrophy (UCMD) is caused by mutations in either COL6A1, COL6A2 or COL6A3 gene, thereby leading to collagen VI deficiency in the ECM. It is known to occur through either recessive or dominant genetic mechanism, the latter most typically by de novo mutations. UCMD is well defined by the clinicopathological hallmarks including distal hyperlaxity, proximal joint contractures, protruding calcanei, scoliosis and respiratory insufficiency. Recent reports have depicted the robust natural history of UCMD; that is, loss of ambulation by early teenage years, rapid decline in respiratory function by 10 years of age and early-onset, rapidly progressive scoliosis. Muscle pathology is characterised by prominent interstitial fibrosis disproportionate to the relative paucity of necrotic and regenerating fibres. To date, treatment for patients is supportive for symptoms such as joint contractures, respiratory failure and scoliosis. There have been clinical trials based on the theory of mitochondrion-mediated myofiber apoptosis or impaired autophagy. Furthermore, the fact that collagen VI producing cells in skeletal muscle are interstitial mesenchymal cells can support proof of concept for stem cell-based therapy.
Topics: Adolescent; Child; Child, Preschool; Collagen Type VI; DNA Mutational Analysis; Disease Progression; Genes, Dominant; Genes, Recessive; Humans; Infant; Infant, Newborn; Mobility Limitation; Muscle, Skeletal; Muscular Dystrophies; Neurologic Examination; Phenotype; Sclerosis
PubMed: 24938411
DOI: 10.1136/jnnp-2013-307052