2,731 results match your criteria Limb-Girdle Muscular Dystrophy

A phase 1b/2a, open-label, multiple ascending dose trial of domagrozumab in FKRP limb-girdle muscular dystrophy.

Muscle Nerve 2021 May 7. Epub 2021 May 7.

Center for Genetic Muscle Disorders, Kennedy Krieger Institute, Baltimore, MD.

Introduction: We report the results of a phase 1b/2a, open-label, multiple ascending dose trial of domagrozumab, a myostatin inhibitor, in patients with FKRP-associated limb-girdle muscular dystrophy.

Methods: Nineteen patients were enrolled and assigned to one of three dosing arms (5 mg/kg, 20mg/kg, or 40mg/kg every 4 weeks). Following 32 weeks of treatment, participants receiving the lowest dose were switched to the highest dose (40mg/kg) for an additional 32 weeks. Read More

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Myocardial strain analysis using cardiac magnetic resonance in patients with calpainopathy.

Orphanet J Rare Dis 2021 Apr 30;16(1):194. Epub 2021 Apr 30.

Department of Internal Medicine and Cardiology, Herzzentrum Dresden Universitätsklinik, Technische Universität Dresden, Dresden, Germany.

Background: Limb-girdle muscular dystrophy (LGMD) is a genetically and clinically heterogeneous group of rare muscular dystrophies. Subtype 2A (LGMD2A) also known as "calpainopathy" is an inherited autosomal recessive gene defect. Cardiac dysfunction is common in several forms of LGMD. Read More

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TRIM32 and Malin in Neurological and Neuromuscular Rare Diseases.

Cells 2021 Apr 6;10(4). Epub 2021 Apr 6.

Department of Life Sciences, University of Trieste, Building Q, Via L. Giorgieri 5, 34127 Trieste, Italy.

Tripartite motif (TRIM) proteins are RING E3 ubiquitin ligases defined by a shared domain structure. Several of them are implicated in rare genetic diseases, and mutations in TRIM32 and TRIM-like malin are associated with Limb-Girdle Muscular Dystrophy R8 and Lafora disease, respectively. These two proteins are evolutionary related, share a common ancestor, and both display NHL repeats at their C-terminus. Read More

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Revisional Surgery After One-Anastomosis Gastric Bypass in a Patient with Limb-Girdle Muscular Dystrophy: Case Report.

Obes Surg 2021 Apr 26. Epub 2021 Apr 26.

Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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Compound heterozygous variants identified in a family with limb-girdle muscular dystrophy recessive 1.

Mol Med Rep 2021 Jun 26;23(6). Epub 2021 Apr 26.

Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.

Limb-girdle muscular dystrophy recessive 1 (LGMDR1), a rare subtype of muscular dystrophy, is characterized by progressive muscle weakness and degeneration with a predominant presentation on the shoulder, pelvic and proximal limb muscles. Variants in calcium-activated neutral proteinase 3 (), which encodes an enzyme, calpain 3, are considered the major cause of LGMDR1. The present study was conducted to identify the variants responsible for clinical symptoms in a Chinese patient with limb-girdle muscular dystrophies (LGMDs) and explore its genotype-phenotype associations. Read More

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Patient-specific iPSC-derived cellular models of LGMDR1.

Stem Cell Res 2021 Apr 8;53:102333. Epub 2021 Apr 8.

Neuroscience Area, Biodonostia Research Institute, San Sebastian, Spain; CIBERNED, Instituto de Salud Carlos III, Madrid, Spain; Department of Neuroscience, University of the Basque Country, San Sebastian, Spain; Department of Neurology, Hospital Universitario Donostia, San Sebastian, Spain. Electronic address:

Limb-girdle muscular dystrophy recessive 1 (LGMDR1) represents one of the most common types of LGMD in the population, where patients develop a progressive muscle degeneration. The disease is caused by mutations in calpain 3 gene, with over 500 mutations reported to date. However, the molecular events that lead to muscle wasting are not clear, nor the reasons for the great clinical variability among patients, and this has so far hindered the development of effective therapies. Read More

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Base editing repairs an SGCA mutation in human primary muscle stem cells.

JCI Insight 2021 Apr 13. Epub 2021 Apr 13.

Muscle Research Unit, Charité University Hospital Berlin, Berlin, Germany.

Skeletal muscle can regenerate from muscle stem cells and their myogenic precursor cell progeny, myoblasts. However, precise gene editing in human muscle stem cells for autologous cell replacement therapies of untreatable genetic muscle diseases has not yet been reported. Loss-of-function mutations in SGCA, encoding α-sarcoglycan, cause limb-girdle muscular dystrophy 2D/R3, an early onset, severe and rapidly progressive form of muscular dystrophy affecting equally girls and boys. Read More

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Over three decades of natural history of limb girdle muscular dystrophy type R1/2A and R2/2B: Mathematical modelling of a multifactorial study.

Neuromuscul Disord 2021 Feb 27. Epub 2021 Feb 27.

Scientific Institute IRCCS E. Medea, NeuroMuscular Unit, Bosisio Parini, LC, Italy.

We aimed to describe the natural history of Limb Girdle Muscular Dystrophy type 2A and 2B over more than three decades by considering muscular strength, motor, cardiac and respiratory function. 428 visits of nineteen 2A and twenty 2B patients were retrospectively analysed through a regression model to create the curves of evolution with disease duration of muscle strength (through Medical Research Council grading), motor function measure scale (D1, D2 and D3 domains) and cardio-pulmonary function tests. Clinically relevant muscular and motor function alterations occurred after the first decade of disease, while mild respiratory function alterations started after the second, with preserved cardiac function. Read More

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February 2021

Crystal structures of β-1,4-N-acetylglucosaminyltransferase 2: structural basis for inherited muscular dystrophies.

Acta Crystallogr D Struct Biol 2021 Apr 30;77(Pt 4):486-495. Epub 2021 Mar 30.

Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.

The canonical O-mannosylation pathway in humans is essential for the functional glycosylation of α-dystroglycan. Disruption of this post-translational modification pathway leads to congenital muscular dystrophies. The first committed step in the construction of a functional matriglycan structure involves the post-translational modification of α-dystroglycan. Read More

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Combined spinal-epidural anesthesia for abdominoplasty and liposuction in Limb-Girdle Muscular Dystrophy: case report.

Braz J Anesthesiol 2021 Apr 3. Epub 2021 Apr 3.

Universidade Federal do Maranhão (UFMA), São Luís, MA, Brazil. Electronic address:

We report the anesthetic management with combined spinal-epidural in a patient with limb-girdle muscular dystrophy type 2A, submitted to abdominoplasty and liposuction. The patient had onset of symptoms at 8 years old, diagnosed by muscular biopsy, presenting muscle weakness in the scapular and pelvic girdles, with reduced mobility. We performed monitorization with noninvasive blood pressure, oximeter, thermometer, and electrocardiogram. Read More

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TRIM32: A Multifunctional Protein Involved in Muscle Homeostasis, Glucose Metabolism, and Tumorigenesis.

Biomolecules 2021 Mar 10;11(3). Epub 2021 Mar 10.

Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS 66506, USA.

Human tripartite motif family of proteins 32 (TRIM32) is a ubiquitous multifunctional protein that has demonstrated roles in differentiation, muscle physiology and regeneration, and tumor suppression. Mutations in TRIM32 result in two clinically diverse diseases. A mutation in the B-box domain gives rise to Bardet-Biedl syndrome (BBS), a disease whose clinical presentation shares no muscle pathology, while mutations in the NHL (NCL-1, HT2A, LIN-41) repeats of TRIM32 causes limb-girdle muscular dystrophy type 2H (LGMD2H). Read More

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Magnetization Transfer Ratio in Lower Limbs of Late Onset Pompe Patients Correlates With Intramuscular Fat Fraction and Muscle Function Tests.

Front Neurol 2021 16;12:634766. Epub 2021 Mar 16.

Neuromuscular Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

Magnetization transfer (MT) imaging exploits the interaction between bulk water protons and protons contained in macromolecules to induce signal changes through a special radiofrequency pulse. MT detects muscle damage in patients with neuromuscular conditions, such as limb-girdle muscular dystrophies or Charcot-Marie-Tooth disease, which are characterized by progressive fiber loss and replacement by fatty tissue. In Pompe disease, in which there is, in addition, an accumulation of glycogen inside the muscle fibers, MT has not been tested yet. Read More

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The birth of informed decisions: Pregnancy and muscular dystrophy.

Muscle Nerve 2021 Mar 24. Epub 2021 Mar 24.

Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, USA.

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[Analysis of genetic variants in five pedigrees affected with Dysferlinopathy].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Mar;38(3):205-209

Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.

Objective: To analyze the clinical phenotype and genetic variants in five Chinese pedigrees affected with Dysferlinopathy.

Methods: Next generation sequencing (NGS) was carried out for the probands from the five pedigrees. Suspected variants were validated by Sanger sequencing. Read More

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Digenic Variants in the and Genes Co-segregating With a Limb-Girdle Muscular Dystrophy in a Han Chinese Family.

Front Neurosci 2021 4;15:601757. Epub 2021 Mar 4.

Center for Experimental Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.

Limb-girdle muscular dystrophies (LGMD) are hereditary genetic disorders characterized by progressive muscle impairment which predominantly include proximal muscle weaknesses in the pelvic and shoulder girdles. This article describes an attempt to identify genetic cause(s) for a LGMD pedigree via a combination of whole exome sequencing and Sanger sequencing. Digenic variants, the titin gene () c. Read More

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Deep phenotyping of an international series of patients with late-onset dysferlinopathy.

Eur J Neurol 2021 Mar 13. Epub 2021 Mar 13.

Nord/Est/Ile-de-France Neuromuscular Reference Center, Institute of Myology, Pitié-Salpêtrière Hospital, APHP, Sorbonne University, Paris, France.

Background: To describe the clinical, pathological, and molecular characteristics of late-onset (LO) dysferlinopathy patients.

Methods: Retrospective series of patients with LO dysferlinopathy, defined by an age at onset of symptoms ≥30 years, from neuromuscular centers in France and the International Clinical Outcome Study for dysferlinopathy (COS). Patients with early-onset (EO) dysferlinopathy (<30 years) were randomly selected from the COS study as a control group, and the North Star Assessment for Dysferlinopathy (NSAD) and Activity Limitation (ACTIVLIM) scores were used to assess functionality. Read More

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Clinical and genetic characterization of PYROXD1-related myopathy patients from Turkey.

Am J Med Genet A 2021 Mar 10. Epub 2021 Mar 10.

Department of Pediatrics, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Congenital myopathies (CMs) are a heterogeneous group of inherited muscle disorders characterized by muscle weakness at birth, while limb-girdle muscular dystrophies (LGMD) have a later onset and slower disease progression. Thus, detailed clinical phenotyping of genetically defined disease entities are required for the full understanding of genotype-phenotype correlations. A recently defined myopathic genetic disease entity is caused by bi-allelic variants in a gene coding for pyridine nucleotide-disulfide oxidoreductase domain 1 (PYROXD1) with unknown substrates. Read More

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Endoplasmic reticulum maintains ion homeostasis required for plasma membrane repair.

J Cell Biol 2021 May;220(5)

Center of Genetic Medicine Research, Children's National Health System, Washington, DC.

Of the many crucial functions of the ER, homeostasis of physiological calcium increase is critical for signaling. Plasma membrane (PM) injury causes a pathological calcium influx. Here, we show that the ER helps clear this surge in cytoplasmic calcium through an ER-resident calcium pump, SERCA, and a calcium-activated ion channel, Anoctamin 5 (ANO5). Read More

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Rimmed vacuoles in late-onset LAMA2-related limb girdle muscular dystrophy.

Acta Neurol Belg 2021 Feb 25. Epub 2021 Feb 25.

Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.

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February 2021

Miyoshi myopathy and limb girdle muscular dystrophy R2 are the same disease.

Neuromuscul Disord 2021 Apr 21;31(4):265-280. Epub 2021 Jan 21.

The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Central Parkway, Newcastle upon Tyne, United Kingdom. Electronic address:

This study aims to determine clinically relevant phenotypic differences between the two most common phenotypic classifications in dysferlinopathy, limb girdle muscular dystrophy R2 (LGMDR2) and Miyoshi myopathy (MMD1). LGMDR2 and MMD1 are reported to involve different muscles, with LGMDR2 showing predominant limb girdle weakness and MMD1 showing predominant distal lower limb weakness. We used heatmaps, regression analysis and principle component analysis of functional and Magnetic Resonance Imaging data to perform a cross-sectional review of the pattern of muscle involvement in 168 patients from the Jain Foundation's international Clinical Outcomes Study for Dysferlinopathy. Read More

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Psychological parameters impact health-related quality of life in mental and physical domains in adults with muscular dystrophy.

Neuromuscul Disord 2021 Apr 19;31(4):328-335. Epub 2021 Jan 19.

Research Centre for Musculoskeletal Science & Sports Medicine, Department of Sport and Exercise Sciences, Manchester Metropolitan University, Manchester M15 6BH, United Kingdom.

The impacts of potentially treatable psychological parameters on quality of life are relatively unreported in adults with Facioscapulohumeral, Becker and Limb-girdle muscular dystrophy. The purpose of this study was to compare quality of life, psychological parameters, and physical function between adults with muscular dystrophy and controls, and to examine relationships among these parameters in muscular dystrophy. Twenty-one adults with muscular dystrophy (n = 7 Becker, n = 8 Facioscapulohumeral, n = 6 Limb-girdle) and ten age-matched controls participated. Read More

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Assessing Dysferlinopathy Patients Over Three Years With a New Motor Scale.

Ann Neurol 2021 May 26;89(5):967-978. Epub 2021 Feb 26.

Department of Neurology Children's National Health System, Washington, DC.

Objective: Dysferlinopathy is a muscular dystrophy with a highly variable clinical presentation and currently unpredictable progression. This variability and unpredictability presents difficulties for prognostication and clinical trial design. The Jain Clinical Outcomes Study of Dysferlinopathy aims to establish the validity of the North Star Assessment for Limb Girdle Type Muscular Dystrophies (NSAD) scale and identify factors that influence the rate of disease progression using NSAD. Read More

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Genetic Modifiers of Hereditary Neuromuscular Disorders and Cardiomyopathy.

Cells 2021 Feb 8;10(2). Epub 2021 Feb 8.

Heart, Lung and Vascular Institute, Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.

Novel genetic variants exist in patients with hereditary neuromuscular disorders (NMD), including muscular dystrophy. These patients also develop cardiac manifestations. However, the association between these gene variants and cardiac abnormalities is understudied. Read More

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February 2021

Next-Generation Sequencing in a Cohort of Asian Indian Patients with the Duchenne Muscular Dystrophy Phenotype: Diagnostic Yield and Mutation Spectrum.

J Pediatr Genet 2021 Mar 8;10(1):23-28. Epub 2020 Jul 8.

MedGenome Labs Ltd., Bengaluru, India.

Multiplex ligation-dependent probe amplification (MLPA) detects exonic deletions and duplications in the gene in around 65 to 70% of patients with the Duchenne muscular dystrophy (DMD) phenotype. This study looks at the diagnostic yield of next-generation sequencing (NGS) and the mutation spectrum in an Asian Indian cohort of MLPA-negative cases with the DMD phenotype. NGS-based sequencing of gene was done in 28 MLPA-negative cases (25 male probands with the DMD phenotype and 3 obligate carrier mothers of deceased affected male patients) and disease-causing variants were identified in 19 (67. Read More

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Cardiac MR Imaging of Muscular Dystrophies.

Curr Probl Diagn Radiol 2021 Jan 9. Epub 2021 Jan 9.

Department of Radiology, University of Colorado - Anschutz Medical Campus, Aurora, CO.

Muscular dystrophies (MDs) are a group of inherited disorders caused by mutations that interfere with muscular structure, contraction, or relaxation. As the cardiac sarcomeric unit shares multiple proteins with the skeletal muscle unit, the heart is affected in several MDs, sometimes without apparent musculoskeletal involvement. Early detection of MD-related cardiomyopathy is crucial as timely initiation of cardioprotective therapy can slow adverse cardiac remodeling. Read More

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January 2021

Subclinical Cardiomyopathy in Miyoshi Myopathy Detected by Late Gadolinium Enhancement Cardiac Magnetic Resonance Imaging.

Int Heart J 2021 ;62(1):186-192

Yong Loo Lin School of Medicine, National University of Singapore.

Dysferlin is a sarcolemmal protein present in muscle cells. It is responsible for muscle membrane repair. Dysferlin gene (DYSF) mutation, resulting in deficiency in this protein, is termed dysferlinopathy. Read More

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February 2021

The outcomes and experience of pregnancy in limb girdle muscular dystrophy type R9.

Muscle Nerve 2021 Jan 27. Epub 2021 Jan 27.

Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.

Introduction: Published information about the experiences of pregnancy in limb girdle muscular dystrophy (LGMD) is limited and does not specify LGMD type, limiting utility. We describe the experience and outcomes of pregnancy in a cohort of women with LGMD type R9 (LGMDR.

Methods: All women 18 y of age or older with a genetic and clinical diagnosis of LGMDR9 who are enrolled in the University of Iowa Wellstone dystroglycanopathy natural history study (clinicaltrials. Read More

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January 2021

ANO5 ensures trafficking of annexins in wounded myofibers.

J Cell Biol 2021 Mar;220(3)

Department of Cell Biology, Emory University School of Medicine, Atlanta, GA.

Mutations in ANO5 (TMEM16E) cause limb-girdle muscular dystrophy R12. Defective plasma membrane repair is a likely mechanism. Using myofibers from Ano5 knockout mice, we show that trafficking of several annexin proteins, which together form a cap at the site of injury, is altered upon loss of ANO5. Read More

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SVIP is a molecular determinant of lysosomal dynamic stability, neurodegeneration and lifespan.

Nat Commun 2021 01 21;12(1):513. Epub 2021 Jan 21.

Department of Biochemistry and Biophysics, Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA, 94158, USA.

Missense mutations in Valosin-Containing Protein (VCP) are linked to diverse degenerative diseases including IBMPFD, amyotrophic lateral sclerosis (ALS), muscular dystrophy and Parkinson's disease. Here, we characterize a VCP-binding co-factor (SVIP) that specifically recruits VCP to lysosomes. SVIP is essential for lysosomal dynamic stability and autophagosomal-lysosomal fusion. Read More

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January 2021

Myostatin inhibition promotes fast fibre hypertrophy but causes loss of AMP-activated protein kinase signalling and poor exercise tolerance in a model of limb-girdle muscular dystrophy R1/2A.

J Physiol 2020 09 24;598(18):3927-3939. Epub 2020 Jul 24.

Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

Key Points: Limb-girdle muscular dystrophy R1 (LGMD R1) is caused by mutations in the CAPN3 gene and is characterized by progressive muscle loss, impaired mitochondrial function and reductions in the slow oxidative gene expression programme. Myostatin is a negative regulator of muscle growth, and its inhibition improves the phenotype in several muscle wasting disorders. The effect of genetic and pharmacological inhibition of myostatin signalling on the disease phenotype in a mouse model of LGMD R1 (CAPN3 knockout mouse-C3KO) was studied. Read More

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September 2020