2,897 results match your criteria Limb-Girdle Muscular Dystrophy

Clinical heterogeneity in epidermolysis bullosa simplex with plectin (PLEC) mutations-A study of six unrelated families from India.

Am J Med Genet A 2022 May 17. Epub 2022 May 17.

Centre for Human Genetics, Biotech Park, Bangalore, Karnataka, India.

Epidermolysis bullosa simplex (EBS) with plectin mutations is a very rare subtype of EB usually associated with pyloric atresia (PA) or muscular dystrophy (MD). We report six unrelated children between ages 4 and 14 years from India with varied clinical manifestations. Only one had PA, and none has developed MD to date. Read More

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Prospective Natural History Study in 24 Adult Patients With LGMDR12 Over 2 Years' Follow-up: Quantitative MRI and Clinical Outcome Measures.

Neurology 2022 May 16. Epub 2022 May 16.

Department of Neurology, University Hospitals Leuven, Leuven, Belgium

Background And Objectives: Limb-Girdle Muscular Dystrophy autosomal recessive type 12 (LGMDR12) is a rare hereditary muscular dystrophy for which outcome measures are currently lacking. We evaluated quantitative MRI and clinical outcome measures to track disease progression, in order to determine which tests could be useful in future clinical trials to evaluate potential therapies.

Methods: We prospectively measured the following outcome measures in all participants at baseline and after 1 and 2 years: six-minute walk distance (6MWD), 10-meter walk test (10MWT), Medical Research Council (MRC) sum scores, Biodex® isometric dynamometry, serum creatine kinase (CK) and 6-point Dixon MRI of the thighs. Read More

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Dual Blockade of Misfolded Alpha-Sarcoglycan Degradation by Bortezomib and Givinostat Combination.

Front Pharmacol 2022 27;13:856804. Epub 2022 Apr 27.

CECS, I-Stem, Corbeil-Essonne, France.

Limb-girdle muscular dystrophy type R3 (LGMD R3) is a rare genetic disorder characterized by a progressive proximal muscle weakness and caused by mutations in the gene encoding alpha-sarcoglycan (α-SG). Here, we report the results of a mechanistic screening ascertaining the molecular mechanisms involved in the degradation of the most prevalent misfolded R77C-α-SG protein. We performed a combinatorial study to identify drugs potentializing the effect of a low dose of the proteasome inhibitor bortezomib on the R77C-α-SG degradation inhibition. Read More

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Unraveling the Molecular Basis of the Dystrophic Process in Limb-Girdle Muscular Dystrophy LGMD-R12 by Differential Gene Expression Profiles in Diseased and Healthy Muscles.

Cells 2022 Apr 30;11(9). Epub 2022 Apr 30.

Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, KU Leuven, and Leuven Brain Institute (LBI), Herestraat 49, 3000 Leuven, Belgium.

Limb-girdle muscular dystrophy R12 (LGMD-R12) is caused by two mutations in anoctamin-5 (). Our aim was to identify genes and pathways that underlie LGMD-R12 and explain differences in the molecular predisposition and susceptibility between three thigh muscles that are severely (semimembranosus), moderately (vastus lateralis) or mildly (rectus femoris) affected in this disease. We performed transcriptomics on these three muscles in 16 male LGMD-R12 patients and 15 age-matched male controls. Read More

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Advanced Gene-Targeting Therapies for Motor Neuron Diseases and Muscular Dystrophies.

Int J Mol Sci 2022 Apr 27;23(9). Epub 2022 Apr 27.

Department of Physiology, School of Medicine, University of Patras, 26504 Patras, Greece.

Gene therapy is a revolutionary, cutting-edge approach to permanently ameliorate or amend many neuromuscular diseases by targeting their genetic origins. Motor neuron diseases and muscular dystrophies, whose genetic causes are well known, are the frontiers of this research revolution. Several genetic treatments, with diverse mechanisms of action and delivery methods, have been approved during the past decade and have demonstrated remarkable results. Read More

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Genetics and muscle pathology in the diagnosis of muscular dystrophies: An update.

Indian J Pathol Microbiol 2022 May;65(Supplement):S259-S270

Department of Medical Genetics, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India.

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. Read More

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Limb-Girdle Muscular Dystrophy R9 due to a Novel Complex Insertion/Duplication Variant in Gene.

Child Neurol Open 2022 Jan-Dec;9:2329048X221097518. Epub 2022 Apr 28.

Division of Neurology, Department of Pediatrics, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, AR, USA.

Limb-girdle muscular dystrophy R9 (LGMD2I, LGMDR9) is an autosomal recessive disorder caused by pathogenic variants in the fukutin-related protein () gene. We describe a 17 year old boy with LGMDR9 whose symptoms began at age 5 years. Muscle histopathology, immunostaining, and western blotting were consistent with a dystroglycanopathy. Read More

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Progression to Loss of Ambulation Among Patients with Autosomal Recessive Limb-girdle Muscular Dystrophy: A Systematic Review.

J Neuromuscul Dis 2022 May 4. Epub 2022 May 4.

Sarepta Therapeutics Inc, Cambridge MA, USA.

BackgroundThe impact of age at autosomal recessive limb girdle muscular dystrophy (LGMDR) onset on progression to loss of ambulation (LOA) has not been well established, particularly by subtype.

Objectives: To describe the characteristics of patients with adult-, late childhood-, and early childhood-onset LGMDR by subtype and characterize the frequency and timing of LOA.

Methods: A systematic review was conducted in MEDLINE, Embase and the Cochrane library. Read More

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Clinical and pathological features of immune-mediated necrotising myopathies in a single-centre muscle biopsy cohort.

BMC Musculoskelet Disord 2022 May 6;23(1):425. Epub 2022 May 6.

China-Japan Friendship School of Clinical Medicine, Peking University, Beijing, 100029, China.

Objective: Immune-mediated necrotising myopathy (IMNM) is a subset of idiopathic inflammatory myopathies (IIM) characterized by significantly elevated creatine kinase level, muscle weakness and predominant muscle fibre necrosis in muscle biopsy. This study aimed to investigate the clinical and pathological characteristics of patients with IMNM in a single-centre muscle biopsy cohort.

Methods: A total of 860 patients who had muscle biopsy reports in our centre from May 2008 to December 2017 were enrolled in this study. Read More

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Comparison of strength testing modalities in dysferlinopathy.

Muscle Nerve 2022 May 4. Epub 2022 May 4.

The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio.

Introduction/aims: Dysferlinopathy demonstrates heterogeneity in muscle weakness between patients, which can progress at different rates over time. Changing muscle strength due to disease progression or from an investigational product is associated with changing functional ability. The purpose of this study was to compare three methods of strength testing used in the Clinical Outcome Study (COS) for dysferlinopathy to understand which method and which muscle groups were most sensitive to change over time. Read More

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2022 HRS expert consensus statement on evaluation and management of arrhythmic risk in neuromuscular disorders.

Heart Rhythm 2022 Apr 26. Epub 2022 Apr 26.

Mayo Clinic College of Medicine, Phoenix, Arizona.

This international multidisciplinary document is intended to guide electrophysiologists, cardiologists, other clinicians, and health care professionals in caring for patients with arrhythmic complications of neuromuscular disorders (NMDs). The document presents an overview of arrhythmias in NMDs followed by detailed sections on specific disorders: Duchenne muscular dystrophy, Becker muscular dystrophy, and limb-girdle muscular dystrophy type 2; myotonic dystrophy type 1 and type 2; Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy type 1B; facioscapulohumeral muscular dystrophy; and mitochondrial myopathies, including Friedreich ataxia and Kearns-Sayre syndrome, with an emphasis on managing arrhythmic cardiac manifestations. End-of-life management of arrhythmias in patients with NMDs is also covered. Read More

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Generation of Calpain-3 knock-out porcine embryos by CRISPR-Cas9 electroporation and intracytoplasmic microinjection of oocytes before insemination.

Theriogenology 2022 Apr 22;186:175-184. Epub 2022 Apr 22.

University of Murcia Dept. Physiology, Murcia, Spain; International Excellence Campus for Higher Education and Research "Campus Mare Nostrum" and Institute for Biomedical Research of Murcia (IMIB-Arrixaca), Murcia, Spain. Electronic address:

Limb girdle muscular dystrophy type R1 (LGMDR1) is an autosomal recessive myopathy described in humans resulting from a deficiency of calpain-3 protein (CAPN3). This disease lacks effective treatment and an appropriate model, so the generation of KO pigs by CRISPR-Cas9 offers a way to better understand disease ethology and to develop novel therapies. Microinjection is the main method described for gene editing by CRISPR-Cas9 in porcine embryo, but electroporation, which allows handling more embryos faster and easier, has also recently been reported. Read More

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[Rare diseases in the differential diagnosis of myalgia].

Schmerz 2022 Apr 29. Epub 2022 Apr 29.

Institut für Digitale Allgemeinmedizin, Uniklinik RWTH Aachen, Aachen, Deutschland.

Myalgia describes pain in the skeletal muscles. According to the current German clinical guidelines from 2020 (AWMF register number: 030/051), the initial diagnostic assessment consists of the anamnesis, clinical examination, electrophysiological examination and standard laboratory tests. Additional special examinations, such as molecular genetic investigations, special laboratory tests, medical imaging and muscle biopsy are only needed in certain cases. Read More

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A Single mtDNA Deletion in Association with a LMNA Gene New Frameshift Variant: A Case Report.

J Neuromuscul Dis 2022 ;9(3):457-462

Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Pisa, Italy.

Background: Proximal muscle weakness may be the presenting clinical feature of different types of myopathies, including limb girdle muscular dystrophy and primary mitochondrial myopathy. LGMD1B is caused by LMNA mutation. It is characterized by progressive weakness and wasting leading to proximal weakness, cardiomyopathy, and hearth conduction block. Read More

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The therapeutic potential of soluble activin type IIB receptor treatment in a limb girdle muscular dystrophy type 2D mouse model.

Neuromuscul Disord 2022 May 7;32(5):419-435. Epub 2022 Mar 7.

Leiden University Medical Center, Department of Human Genetics, Leiden, the Netherlands. Electronic address:

Limb girdle muscular dystrophy type 2D (LGMD2D) is characterized by progressive weakening of muscles in the hip and shoulder girdles. It is caused by a mutation in the α-sarcoglycan gene and results in absence of α-sarcoglycan in the dystrophin-glycoprotein complex. The activin type IIB receptor is involved in the activin/myostatin pathway, with myostatin being a negative regulator of muscle growth. Read More

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Modeling Patient-Specific Muscular Dystrophy Phenotypes and Therapeutic Responses in Reprogrammed Myotubes Engineered on Micromolded Gelatin Hydrogels.

Front Cell Dev Biol 2022 6;10:830415. Epub 2022 Apr 6.

Department of Microbiology Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, United States.

models of patient-derived muscle allow for more efficient development of genetic medicines for the muscular dystrophies, which often present mutation-specific pathologies. One popular strategy to generate patient-specific myotubes involves reprogramming dermal fibroblasts to a muscle lineage through MyoD induction. However, creating physiologically relevant, reproducible tissues exhibiting multinucleated, aligned myotubes with organized striations is dependent on the introduction of physicochemical cues that mimic the native muscle microenvironment. Read More

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Novel Variants of in Two Patients With Limb Girdle Muscular Dystrophy: Case Report.

Front Neurol 2022 8;13:868655. Epub 2022 Apr 8.

Department of Neurology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.

Here we report on two unrelated adult patients presenting with Limb girdle muscular dystrophy who were found to have novel variants in . Both patients had prominent weakness of their proximal lower limbs with mild weakness of elbow flexion and markedly elevated creatine kinase. Next generation sequencing using a custom-designed neuromuscular panel was performed in both patients. Read More

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Expanding the Phenotype of B3GALNT2-Related Disorders.

Genes (Basel) 2022 04 14;13(4). Epub 2022 Apr 14.

Center for Medical Genetics, Ghent University Hospital, 9000 Ghent, Belgium.

Dystroglycanopathies are a group of congenital muscular dystrophies (CMDs) that include a broad phenotypic spectrum ranging from late-onset limb-girdle muscular dystrophy to severe muscle-eye-brain disease, Walker-Warburg syndrome, and Fukuyama congenital muscular dystrophy. In addition to clinical heterogeneity, CMDs are characterized by genetic heterogeneity. To date, 18 genes have been associated with CMDs. Read More

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The Cure VCP Scientific Conference 2021: Molecular and clinical insights into neurodegeneration and myopathy linked to multisystem proteinopathy-1 (MSP-1).

Neurobiol Dis 2022 Jul 8;169:105722. Epub 2022 Apr 8.

Department of Developmental Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA, United States of America. Electronic address:

The 2021 VCP Scientific Conference took place virtually from September 9-10, 2021. This conference, planned and organized by the nonprofit patient advocacy group Cure VCP Disease, Inc. (https://www. Read More

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Serum miRNAs as biomarkers for the rare types of muscular dystrophy.

Neuromuscul Disord 2022 Apr 11;32(4):332-346. Epub 2022 Mar 11.

Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, PO Box 23462, Nicosia 1683, Cyprus; Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, PO Box 23462, Nicosia 1683, Cyprus. Electronic address:

Muscular dystrophies are a group of disorders that cause progressive muscle weakness. There is an increasing interest for the development of biomarkers for these disorders and specifically for Duchene Muscular Dystrophy. Limited research however, has been performed on the biomarkers' development for the most rare muscular dystrophies, like the Facioscapulohumeral Muscular Dystrophy, Limb-Girdle Muscular Dystrophy and Myotonic Dystrophy type 2. Read More

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Circulating small RNA signatures differentiate accurately the subtypes of muscular dystrophies: small-RNA next-generation sequencing analytics and functional insights.

RNA Biol 2022 31;19(1):507-518. Epub 2021 Dec 31.

Department of Molecular Genetics, Function & Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.

Muscular dystrophies are a group of rare and severe inherited disorders mainly affecting the muscle tissue. Duchene Muscular Dystrophy, Myotonic Dystrophy types 1 and 2, Limb Girdle Muscular Dystrophy and Facioscapulohumeral Muscular Dystrophy are some of the members of this family of disorders. In addition to the current diagnostic tools, there is an increasing interest for the development of novel non-invasive biomarkers for the diagnosis and monitoring of these diseases. Read More

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Three-year quantitative magnetic resonance imaging and phosphorus magnetic resonance spectroscopy study in lower limb muscle in dysferlinopathy.

J Cachexia Sarcopenia Muscle 2022 Apr 3. Epub 2022 Apr 3.

Magnetic Resonance Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.

Background: Natural history studies in neuromuscular disorders are vital to understand the disease evolution and to find sensitive outcome measures. We performed a longitudinal assessment of quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy ( P MRS) outcome measures and evaluated their relationship with function in lower limb skeletal muscle of dysferlinopathy patients.

Methods: Quantitative MRI/ P MRS data were obtained at 3 T in two different sites in 54 patients and 12 controls, at baseline, and three annual follow-up visits. Read More

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Deficiency in Zebrafish Leads to ROS Production and Mitophagy, and Idebenone Improves its Phenotypes.

Front Cell Dev Biol 2022 15;10:836464. Epub 2022 Mar 15.

Department of Neurology and Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital, Shandong University, Jinan, China.

Limb-girdle muscular dystrophy 2G (LGMD2G) is a subtype of limb-girdle muscular dystrophy. However, the disease's mechanisms are still not fully understood, and no established therapeutic targets have been found. Using a morpholino-based knockdown approach, we established an LGMD2G zebrafish model. Read More

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Current and Future Therapeutic Strategies for Limb Girdle Muscular Dystrophy Type R1: Clinical and Experimental Approaches.

Pathophysiology 2021 May 18;28(2):238-249. Epub 2021 May 18.

Department of Medical Genetics, Medical School, Erciyes University, 38039 Kayseri, Turkey.

Limb girdle muscular dystrophy type R1 disease is a progressive disease that is caused by mutations in the gene and involves the extremity muscles of the hip and shoulder girdle. The CAPN3 protein has proteolytic and non-proteolytic properties. The functions of the CAPN3 protein that have been determined so far can be listed as remodeling and combining contractile proteins in the sarcomere with the substrates with which it interacts, controlling the Ca flow in and out through the sarcoplasmic reticulum, and regulation of membrane repair and muscle regeneration. Read More

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Assessing the Relationship of Patient Reported Outcome Measures With Functional Status in Dysferlinopathy: A Rasch Analysis Approach.

Front Neurol 2022 10;13:828525. Epub 2022 Mar 10.

Charite Muscle Research Unit, Experimental and Clinical Research Center, A Joint Cooperation of the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine, Berlin, Germany.

Dysferlinopathy is a muscular dystrophy with a highly variable functional disease progression in which the relationship of function to some patient reported outcome measures (PROMs) has not been previously reported. This analysis aims to identify the suitability of PROMs and their association with motor performance.Two-hundred and four patients with dysferlinopathy were identified in the Jain Foundation's Clinical Outcome Study in Dysferlinopathy from 14 sites in 8 countries. Read More

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The effects of home exercise program on limb-girdle disease: a cohort study.

Folia Neuropathol 2022 ;60(1):48-59

Molecular Biology and Genetics Department, Faculty of Medicine, Dicle University, Diyarbakır, Turkey.

This study aims to demonstrate the effectiveness of rehabilitation in patients with limb-girdle disease, who were given a home exercise program and called for follow-up in certain periods by observing the functional areas of the shoulder and pelvic groups every six months. Suitable statistical methods were conducted. Descriptive findings and continuous variables regarding the patients were presented. Read More

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Evaluating Therapeutic Activity of Galectin-1 in Sarcolemma Repair of Skeletal Muscle.

Methods Mol Biol 2022 ;2442:663-683

Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.

Galectin-1 is a small (14.5 kDa) multifunctional protein with cell-cell and cell-ECM adhesion due to interactions with the carbohydrate recognition domain (CRD). In two types of muscular dystrophies, this lectin protein has shown therapeutic properties, including positive regulation of skeletal muscle differentiation and regeneration. Read More

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Targeting the Ubiquitin-Proteasome System in Limb-Girdle Muscular Dystrophy With CAPN3 Mutations.

Front Cell Dev Biol 2022 2;10:822563. Epub 2022 Mar 2.

Group of Neuroscience, Departments of Pediatrics and Neuroscience, Faculty of Medicine and Nursing, Hospital Donostia, UPV/EHU, San Sebastian, Spain.

LGMDR1 is caused by mutations in the gene that encodes calpain 3 (CAPN3), a non-lysosomal cysteine protease necessary for proper muscle function. Our previous findings show that CAPN3 deficiency leads to reduced SERCA levels through increased protein degradation. This work investigates the potential contribution of the ubiquitin-proteasome pathway to increased SERCA degradation in LGMDR1. Read More

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LGMD D2 TNPO3-Related: From Clinical Spectrum to Pathogenetic Mechanism.

Front Neurol 2022 4;13:840683. Epub 2022 Mar 4.

Department of Biomedical and Neuromotor Sciences-DIBINEM, Alma Mater Studiorum University of Bologna, Bologna, Italy.

Limb-girdle muscular dystrophies (LGMDs) are clinically and genetically heterogeneous diseases presenting with a wide clinical spectrum. Autosomal dominant LGMDs represent about 10-15% of LGMDs and include disorders due to defects of DNAJB6, transportin-3 (TNPO3), HNRNPDL, Calpain-3 (CAPN3), and Bethlem myopathy. This review article aims to describe the clinical spectrum of LGMD D2 TNPO3-related, a rare disease due to heterozygous mutation in the gene. Read More

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A new missense variant in RAB3GAP2 in a family with muscular dystrophy-short stature and defective autophagy: An expansion of the micro/Martsolf spectrum or a new phenotype?

Am J Med Genet A 2022 Mar 11. Epub 2022 Mar 11.

Research Unit, Genetics Department, Institute of Ophthalmology "Conde de Valenciana", Mexico City, Mexico.

We describe a sibling pair of Mennonite origin born from consanguineous parentage with a likely new phenotype of limb-girdle muscular dystrophy, short stature, ptosis, and tracheomalacia. Exome sequencing in the affected subjects identified a novel homozygous RAB3GAP2 missense variant as the potential causal variant. As RAB3GAP2 has been recently shown to be involved in the autophagy process, we analyzed patient-derived fibroblasts by fluorescence microscopy and demonstrated defective autophagic flux under rapamycin and serum starvation conditions when compared with wild-type cells. Read More

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