2,594 results match your criteria Limb-Girdle Muscular Dystrophy


Glycogenin-1 deficiency mimicking limb-girdle muscular dystrophy.

Mol Genet Metab Rep 2020 Sep 24;24:100597. Epub 2020 May 24.

Neurology Department, Raymond Poincaré University Hospital, Garches, APHP, France.

Glycogen storage disease type XV (GSD XV) is a recently described muscle glycogenosis due to glycogenin-1 () deficiency characterized by the presence of polyglucosan bodies on muscle biopsy (Polyglucosan body myopathy-2, PGBM2). Here we describe a 44 year-old man with limb-girdle muscle weakness mimicking a limb-girdle muscular dystrophy (LGMD), and early onset exertional myalgia. Neurologic examination revealed a waddling gait with hyperlordosis, bilateral asymmetric scapular winging, mild asymmetric deltoid and biceps brachii weakness, and pelvic-girdle weakness involving the gluteal muscles and, to a lesser extent, the quadriceps. Read More

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http://dx.doi.org/10.1016/j.ymgmr.2020.100597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251390PMC
September 2020

Collagen VI-related limb-girdle syndrome caused by frequent mutation in COL6A3 gene with conflicting reports of pathogenicity.

Neuromuscul Disord 2020 Apr 18. Epub 2020 Apr 18.

Latvian Biomedical Research and Study Centre, Ratsupites 1, Riga LV-1067, Latvia; Medical Genetics department, CHUQ, 2705 Blvd Laurier, Quebec City, Canada.

Recently the scientific community has started to view Bethlem myopathy 1 and Ullrich congenital muscular dystrophy as two extremes of a collagen VI-related myopathy spectrum rather than two separate entities, as both are caused by mutations in one of the collagen VI genes. Here we report three individuals in two families who are homozygous for a COL6A3 mutation (c.7447A> G; p. Read More

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http://dx.doi.org/10.1016/j.nmd.2020.03.010DOI Listing

Frizzled related protein deficiency impairs muscle strength, gait and calpain 3 levels.

Orphanet J Rare Dis 2020 May 24;15(1):119. Epub 2020 May 24.

Biodonostia Health Research Institute, Neurosciences Area, San Sebastian, Spain.

Background: Limb-girdle muscular dystrophy recessive 1 calpain3-related (LGMDR1), previously known as LGMD2A, is a disease caused by mutations in the CAPN3 gene. It is characterized by progressive weakness and muscle degeneration. Frizzled related protein (FRZB), upregulated in LGMDR1, was identified as a key regulator of the crosstalk between Wnt and integrin signalling pathways. Read More

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http://dx.doi.org/10.1186/s13023-020-01372-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245871PMC

Anti-HMGCR myopathy mimicking limb-girdle muscular dystrophy and the response to Rituximab.

Clin Neurol Neurosurg 2020 Apr 28;194:105871. Epub 2020 Apr 28.

University of Missouri Health Care, 1 Hospital Drive, Columbia, MO 65212, United States.

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http://dx.doi.org/10.1016/j.clineuro.2020.105871DOI Listing

Pauses in atrial rhythm in a patient with limb-girdle muscular dystrophy: A case report.

J Electrocardiol 2020 May 11;60:209-211. Epub 2020 May 11.

Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.

A 58-year-old woman with a history of multi-origin atrial tachycardia and limb-girdle muscular dystrophy was treated for presyncope caused by pauses in atrial rhythm. A dual-chamber pacemaker was implanted. The low-voltage area extended broadly, but 10-V pacing could not capture the large right atrium, including the right atrial appendage, except the coronary sinus ostium. Read More

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http://dx.doi.org/10.1016/j.jelectrocard.2020.05.003DOI Listing

Longitudinal functional and imaging outcome measures in FKRP limb-girdle muscular dystrophy.

BMC Neurol 2020 May 19;20(1):196. Epub 2020 May 19.

Center for Genetic Muscle Disorders, Hugo W. Moser Research Institute at Kennedy Krieger Institute, 716 North Broadway, Room 411, Baltimore, MD, 21205, USA.

Background: Pathogenic variants in the FKRP gene cause impaired glycosylation of α-dystroglycan in muscle, producing a limb-girdle muscular dystrophy with cardiomyopathy. Despite advances in understanding the pathophysiology of FKRP-associated myopathies, clinical research in the limb-girdle muscular dystrophies has been limited by the lack of normative biomarker data to gauge disease progression.

Methods: Participants in a phase 2 clinical trial were evaluated over a 4-month, untreated lead-in period to evaluate repeatability and to obtain normative data for timed function tests, strength tests, pulmonary function, and body composition using DEXA and whole-body MRI. Read More

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http://dx.doi.org/10.1186/s12883-020-01774-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236878PMC

Inhibition of DNAJ-HSP70 interaction improves strength in muscular dystrophy.

J Clin Invest 2020 May 19. Epub 2020 May 19.

Department of Neurology, Washington University School of Medicine, St. Louis, United States of America.

Dominant mutations in the HSP70 co-chaperone DNAJB6 cause a late onset muscle disease termed limb girdle muscular dystrophy type D1 (LGMDD1), which is characterized by protein aggregation and vacuolar myopathology. Disease mutations reside within the G/F domain of DNAJB6, but the molecular mechanisms underlying dysfunction are not well understood. Using yeast, cell culture, and mouse models of LGMDD1, we found that the toxicity associated with disease-associated DNAJB6 required its interaction with HSP70, and that abrogating this interaction genetically or with small molecules was protective. Read More

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http://dx.doi.org/10.1172/JCI136167DOI Listing

Differential diagnosis of vacuolar myopathies in the NGS era.

Brain Pathol 2020 May 17. Epub 2020 May 17.

Institute of Neuropathology, RWTH Aachen University, Aachen, Germany.

Altered autophagy accompanied by abnormal autophagic (rimmed) vacuoles detectable by light and electron microscopy is a common denominator of many familial and sporadic non-inflammatory muscle diseases. Even in the era of next generation sequencing (NGS), late-onset vacuolar myopathies remain a diagnostic challenge. We identified 32 adult vacuolar myopathy patients from 30 unrelated families, studied their clinical, histopathological and ultrastructural characteristics and performed genetic testing in index patients and relatives using Sanger sequencing and NGS including whole exome sequencing (WES). Read More

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http://dx.doi.org/10.1111/bpa.12864DOI Listing

Update on Muscular Dystrophies with Focus on Novel Treatments and Biomarkers.

Curr Neurol Neurosci Rep 2020 May 14;20(6):14. Epub 2020 May 14.

Department of Neurology, Boston Children's Hospital, 300 Longwood Ave, Boston, MA, 02116, USA.

Purpose Of Review: Muscular dystrophies are a heterogeneous group of inherited muscular disorders characterized by progressive muscle weakness and in many cases cardiac and respiratory muscle involvement. Historically, these disorders are considered incurable with grave prognoses. The genes responsible for most muscular dystrophies are known, and early diagnosis is achievable with proper clinical recognition and advanced genetic testing. Read More

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http://dx.doi.org/10.1007/s11910-020-01034-6DOI Listing

HNRNPDL-related limb girdle muscular dystrophy in a Spanish family with scapulo-peroneal phenotype, the first family in Europe.

J Neurol Sci 2020 May 1;414:116875. Epub 2020 May 1.

Neuromuscular Reference Centre ERN EURO-NMD and Research Group on NMD and Ataxias, IIS La Fe and CIBERER, Hospital Universitari i Politècnic La Fe, Avenida Fernando Abril Martorell 106, floor 5, tower C, 46026, Valencia, Spain. Electronic address:

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http://dx.doi.org/10.1016/j.jns.2020.116875DOI Listing

The genetic profile of dysferlinopathy in a cohort of 209 cases: genotype-phenotype relationship and a hotspot on the inner DysF domain.

Hum Mutat 2020 May 12. Epub 2020 May 12.

Departments of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Dysferlinopathy is a group of autosomal recessive muscular dystrophies caused by variants in the dysferlin gene (DYSF), with variable proximal and distal muscle involvement. We performed DYSF gene analyses of 200 cases suspected of having dysferlinopathy (cohort 1), and identified diagnostic variants in 129/200 cases, including 19 novel variants. To achieve a comprehensive genetic profile of dysferlinopathy, we analyzed the variant data from 209 affected cases from unrelated 209 families including 80 previously diagnosed and 129 newly diagnosed cases (cohort 2). Read More

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http://dx.doi.org/10.1002/humu.24036DOI Listing

Anoctamin 5 (ANO5) muscular dystrophy-three different phenotypes and a new histological pattern.

Neurol Sci 2020 May 12. Epub 2020 May 12.

Muscle Research Unit, Internal Medicine Service, Hospital Clínic de Barcelona, Universidad de Barcelona and CIBERER, C/Villarroel, 170 08036, Barcelona, Spain.

Objective: Anoctamin 5 (ANO5) is a putative intracellular calcium-activated chloride channel. Recessive mutations in ANO5 may present from asymptomatic hyperCKemia and exercise-induced myalgia to proximal and/or distal muscle weakness. Here we describe the clinical, pathological, and molecular findings of three unrelated patients with ANO5-related muscular dystrophy. Read More

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http://dx.doi.org/10.1007/s10072-020-04453-yDOI Listing

Genetic Counseling and NGS Screening for Recessive LGMD2A Families.

High Throughput 2020 May 10;9(2). Epub 2020 May 10.

Genomic Medicine Laboratory UILDM, Santa Lucia Foundation, 00179 Rome, Italy.

Genetic counseling applied to limb-girdle muscular dystrophies (LGMDs) can be very challenging due to their clinical and genetic heterogeneity and the availability of different molecular assays. Genetic counseling should therefore be addressed to select the most suitable approach to increase the diagnostic rate and provide an accurate estimation of recurrence risk. This is particularly true for families with a positive history for recessive LGMD, in which the presence of a known pathogenetic mutation segregating within the family may not be enough to exclude the risk of having affected children without exploring the genetic background of phenotypically unaffected partners. Read More

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http://dx.doi.org/10.3390/ht9020013DOI Listing

Variants in and Not Necessarily Indicate Familial Amyotrophic Lateral Sclerosis or Limb Girdle Muscular Dystrophy 1G in Acute Muscular Respiratory Failure.

J Neurosci Rural Pract 2020 Apr 2;11(2):353-354. Epub 2020 May 2.

Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria.

Genetic work-up is useful for the identification of a primary myopathy. However, even sophisticated genetic methods may fail to detect the underlying cause of myopathy as in the following case. The patient is a 52-year-old female with a history of epilepsy, arterial hypertension, atrial flutter requiring cardioversion, ablation, and anticoagulation, coronary heart disease, hyperlipidemia, and hyper-CKemia. Read More

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http://dx.doi.org/10.1055/s-0040-1709375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195953PMC

Characteristic muscle signatures assessed by quantitative MRI in patients with Bethlem myopathy.

J Neurol 2020 May 3. Epub 2020 May 3.

Copenhagen Neuromuscular Center, Section 3342, Department of Neurology, University of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.

Using MRI, the main aim was to (1) map the pattern of muscle involvement by assessing fat fraction and (2) investigate frequency of target and sandwich signs in 42 muscles of patients with Bethlem myopathy (BM). Fifteen BM patients were included. Results were compared to findings in 8 healthy controls and 50 patients with four other types of muscular dystrophies. Read More

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http://dx.doi.org/10.1007/s00415-020-09860-xDOI Listing

Duchenne muscular dystrophy-like phenotype in an LGMD2I patient with novel gene variants.

Hum Genome Var 2020 20;7:12. Epub 2020 Apr 20.

1Division of Clinical Genetics, Tottori University Hospital, Yonago, Japan.

A 32-year-old man initially received a diagnosis of Duchenne muscular dystrophy (DMD). Genetic analysis revealed two novel heterozygous variants: c.169G>A (p. Read More

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http://dx.doi.org/10.1038/s41439-020-0099-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171098PMC

Novel CAPN3 variant associated with an autosomal dominant calpainopathy.

Neuropathol Appl Neurobiol 2020 Apr 28. Epub 2020 Apr 28.

Aix-Marseille Université, INSERM, Marseille Medical Genetics, U1251, Marseille, France.

Aims: The most common autosomal recessive limb girdle muscular dystrophy is associated with the CAPN3 gene. The exclusively recessive inheritance of this disorder has been recently challenged by the description of the recurrent variants, c.643_663del21 [p. Read More

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http://dx.doi.org/10.1111/nan.12624DOI Listing

Global FKRP Registry: observations in more than 300 patients with Limb Girdle Muscular Dystrophy R9.

Ann Clin Transl Neurol 2020 May 28;7(5):757-766. Epub 2020 Apr 28.

John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.

Objective: The Global FKRP Registry is a database for individuals with conditions caused by mutations in the Fukutin-Related Protein (FKRP) gene: limb girdle muscular dystrophy R9 (LGMDR9, formerly LGMD2I) and congenital muscular dystrophies MDC1C, Muscle-Eye-Brain Disease and Walker-Warburg Syndrome. The registry seeks to further understand the natural history and prevalence of FKRP-related conditions; aid the rapid identification of eligible patients for clinical studies; and provide a source of information to clinical and academic communities.

Methods: Registration is patient-initiated through a secure online portal. Read More

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http://dx.doi.org/10.1002/acn3.51042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261761PMC

Facioscapulohumeral muscular dystrophy 1 patients participating in the UK FSHD registry can be subdivided into 4 patterns of self-reported symptoms.

Neuromuscul Disord 2020 Apr 12;30(4):315-328. Epub 2020 Mar 12.

John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Centre for Life, Newcastle NE1 3BZ, UK.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant incurable skeletal muscle disease. FSHD1 constitutes 95% of cases and is linked to truncation of the D4Z4 macrosatellite at 4q35. In most cases the condition initially presents with facial and proximal weakness of the upper limbs, but over the course of the disease involves lower limb and truncal muscles. Read More

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http://dx.doi.org/10.1016/j.nmd.2020.03.001DOI Listing

Efficient engraftment of pluripotent stem cell-derived myogenic progenitors in a novel immunodeficient mouse model of limb girdle muscular dystrophy 2I.

Skelet Muscle 2020 Apr 22;10(1):10. Epub 2020 Apr 22.

Lillehei Heart Institute, Department of Medicine, University of Minnesota, 4-128 CCRB, 2231 6th St. SE, Minneapolis, MN, 55455, USA.

Background: Defects in α-dystroglycan (DG) glycosylation characterize a group of muscular dystrophies known as dystroglycanopathies. One of the key effectors in the α-DG glycosylation pathway is the glycosyltransferase fukutin-related protein (FKRP). Mutations in FKRP lead to a large spectrum of muscular dystrophies, including limb girdle muscular dystrophy 2I (LGMD2I). Read More

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http://dx.doi.org/10.1186/s13395-020-00228-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175515PMC

Outcomes of scapulothoracic fusion in facioscapulohumeral muscular dystrophy: A systematic review.

Shoulder Elbow 2020 Apr 14;12(2):75-90. Epub 2019 Aug 14.

Division of Orthopaedic Surgery, Department of Surgery, McMaster University, Hamilton, Canada.

Background: Facioscapulohumeral muscular dystrophy (FSHD) is a rare condition associated with selective weakness of the muscles of the upper arm, face, and shoulder girdle, negatively affecting daily activities. Scapulothoracic arthrodesis may restore shoulder function and improve quality of life. The purpose of this review is to evaluate the outcomes and complications of scapulothoracic arthrodesis in FSHD patients. Read More

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http://dx.doi.org/10.1177/1758573219866195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153204PMC

Reporting a rare form of myopathy, myopathy with extrapyramidal signs, in an Iranian family using next generation sequencing: a case report.

BMC Med Genet 2020 Apr 15;21(1):77. Epub 2020 Apr 15.

Medical Genetics Lab, Kawsar Human Genetics Research Center, No. 41, Majlesi St., Valieasr Ave, Tehran, Iran.

Background: Myopathy with extrapyramidal signs (MPXPS) is an autosomal recessive mitochondrial disorder which is caused by mutation in mitochondrial calcium uptake 1 (MICU1) gene located on chromosome 10q22.1. Next Generation Sequencing (NGS) technology is the most effective method for identification of pathogenic variants with the ability to overcome some limitations which Sanger sequencing may encountered. Read More

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http://dx.doi.org/10.1186/s12881-020-01016-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158096PMC

Self-reported physical activity in people with limb-girdle muscular dystrophy and Charcot-Marie-Tooth disease in Norway.

BMC Musculoskelet Disord 2020 Apr 13;21(1):235. Epub 2020 Apr 13.

Institute of Health and Society, University of Oslo, P.O. Box 1089, N-0318, Oslo, Blindern, Norway.

Background: Physical activity is associated with positive health effects, but individuals with neuromuscular disease (NMD) may experience constraints being physically active. There is a gap in the literature on the activity level of people with NMDs, and therefore we did a study to determine the physical activity level in people with Limb-Girdle muscular dystrophy (LGMD) and Charcot-Marie-Tooth disease (CMT).

Methods: This study used a cross-sectional design to obtain self-reported physical activity and sitting time among individuals with LGMD and CMT who were recruited from the Norwegian registry for hereditary and congenital neuromuscular diseases. Read More

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http://dx.doi.org/10.1186/s12891-020-03246-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155285PMC

Congenital myasthenic syndrome due to DOK7 mutation in a cohort of patients with 'unexplained' limb-girdle muscular weakness.

J Clin Neurosci 2020 May 29;75:195-198. Epub 2020 Mar 29.

Service of Neuromuscular Disorders, Division of Neurology, Department of Internal Medicine, Hospital de Clínicas, Universidade Federal do Paraná (UFPR), Curitiba, Brazil. Electronic address:

Congenital myasthenic syndromes (CMS) associated with pathogenic variants in the DOK7 gene (DOK7-CMS) have phenotypic overlap with other neuromuscular disorders associated with limb-girdle muscular weakness (LGMW). Genetic analysis of the most common mutation (c.1124_1127dupTGCC) in DOK7 was performed in 34 patients with "unexplained" LGMW associated with non-specific changes in muscle biopsy. Read More

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http://dx.doi.org/10.1016/j.jocn.2020.01.080DOI Listing

A muscle-specific calpain, CAPN3, forms a homotrimer.

Biochim Biophys Acta Proteins Proteom 2020 Jul 19;1868(7):140411. Epub 2020 Mar 19.

From Calpain Project, Department of Advanced Science for Biomolecules, Tokyo Metropolitan Institute of Medical Science (TMiMS), 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan. Electronic address:

Calpain-3 (CAPN3), a 94-kDa member of the calpain protease family, is abundant in skeletal muscle. Mutations in the CAPN3 gene cause limb girdle muscular dystrophy type 2A, indicating that CAPN3 plays important roles in muscle physiology. CAPN3 has several unique features. Read More

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http://dx.doi.org/10.1016/j.bbapap.2020.140411DOI Listing

Combined Use of CFTR Correctors in LGMD2D Myotubes Improves Sarcoglycan Complex Recovery.

Int J Mol Sci 2020 Mar 6;21(5). Epub 2020 Mar 6.

Department of Biomedical Sciences, University of Padova, Via U. Bassi 58/b 35131 Padova, Italy.

Sarcoglycanopathies are rare limb girdle muscular dystrophies, still incurable, even though symptomatic treatments may slow down the disease progression. Most of the disease-causing defects are missense mutations leading to a folding defective protein, promptly removed by the cell's quality control, even if possibly functional. Recently, we repurposed small molecules screened for cystic fibrosis as potential therapeutics in sarcoglycanopathy. Read More

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http://dx.doi.org/10.3390/ijms21051813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084537PMC

HNK-1 Sulfotransferase modulates α-dystroglycan glycosylation by 3-O-sulfation of glucuronic acid on matriglycan.

Glycobiology 2020 Mar 9. Epub 2020 Mar 9.

Complex Carbohydrate Research Center.

Mutations in multiple genes required for proper O-mannosylation of α-dystroglycan are causal for congenital/limb-girdle muscular dystrophies and abnormal brain development in mammals. Previously, we and others further elucidated the functional O-mannose glycan structure that is terminated by matriglycan, [(-GlcA-β3-Xyl-α3-)n]. This repeating disaccharide serves as a receptor for proteins in the extracellular matrix. Read More

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http://dx.doi.org/10.1093/glycob/cwaa024DOI Listing

A hospital based epidemiological study of genetically determined muscle disease in south western Norway.

Neuromuscul Disord 2020 Mar 4;30(3):181-185. Epub 2020 Feb 4.

Department of Clinical Medicine, University of Bergen, Norway; Department of Neurology, Haukeland University Hospital, Bergen, Norway. Electronic address:

We determined the prevalence of genetically determined neuromuscular diseases in adult Norwegian patients from Hordaland County. We identified patients using International Classification of Disease codes registered in our hospital database and reviewed patient notes to ensure diagnostic accuracy. To ensure maximal ascertainment, we screened both inpatient and outpatient contacts from two 5-year periods 01. Read More

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http://dx.doi.org/10.1016/j.nmd.2020.01.006DOI Listing

Functions of Vertebrate Ferlins.

Cells 2020 Feb 25;9(3). Epub 2020 Feb 25.

Department of Child and Adolescent Health, University Medical Center Göttingen, 37075 Göttingen, Germany.

Ferlins are multiple-C2-domain proteins involved in Ca2+-triggered membrane dynamics within the secretory, endocytic and lysosomal pathways. In bony vertebrates there are six ferlin genes encoding, in humans, dysferlin, otoferlin, myoferlin, Fer1L5 and 6 and the long noncoding RNA Fer1L4. Mutations in (dysferlin) can cause a range of muscle diseases with various clinical manifestations collectively known as dysferlinopathies, including limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy. Read More

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http://dx.doi.org/10.3390/cells9030534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140416PMC
February 2020

Caveolin-3 deficiency associated with the dystrophy P104L mutation impairs skeletal muscle mitochondrial form and function.

J Cachexia Sarcopenia Muscle 2020 Feb 23. Epub 2020 Feb 23.

Division of Cell Signalling and Immunology, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee, UK.

Background: Caveolin-3 (Cav3) is the principal structural component of caveolae in skeletal muscle. Dominant pathogenic mutations in the Cav3 gene, such as the Limb Girdle Muscular Dystrophy-1C (LGMD1C) P104L mutation, result in substantial loss of Cav3 and myopathic changes characterized by muscle weakness and wasting. We hypothesize such myopathy may also be associated with disturbances in mitochondrial biology. Read More

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http://dx.doi.org/10.1002/jcsm.12541DOI Listing
February 2020

Limb-girdle Muscular Dystrophy and Therapy: Insights into Cell and Gene-based Approaches.

Curr Gene Ther 2020 ;19(6):386-394

Department of Medical Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

The Limb-Girdle Muscular Dystrophies (LGMD) are genetically heterogeneous disorders, responsible for muscle wasting and severe form of dystrophies. Despite the critical developments in the insight and information of pathomechanisms of limb-girdle muscular dystrophy, any definitive treatments do not exist, and current strategies are only based on the improvement of the signs of disorder and to enhance the life quality without resolving an underlying cause. There is a crucial relationship between pharmacological therapy and different consequences; therefore, other treatment strategies will be required. Read More

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http://dx.doi.org/10.2174/1566523220666200218113526DOI Listing
January 2020

A novel noncoding mutation in early onset limb-girdle muscular dystrophy.

Neurol Genet 2020 Feb 26;6(1):e388. Epub 2019 Dec 26.

Department of Pediatrics (E.S., A.A., A.V.), Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock; MNG Laboratories (H.M., P.N.), Atlanta, GA; Department of Pathology (S.A.M., M.O.C.), University of Iowa; Department of Pathology (M.G.), University of Arkansas for Medical Sciences, Little Rock; Departments of Pediatrics and Physical Medicine and Rehabilitation (V.S.), Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock.

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http://dx.doi.org/10.1212/NXG.0000000000000388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940478PMC
February 2020

Modulators of calpain activity: inhibitors and activators as potential drugs.

Expert Opin Drug Discov 2020 Apr 5;15(4):471-486. Epub 2020 Feb 5.

Department of Organic Chemistry, Institute of Chemistry, Eötvös Loránd University, Budapest, Hungary.

: Calpains are intracellular Ca-dependent cysteine proteases with 15 known members in the enzyme family. They act as regulatory enzymes, their cleavage modifying the function of their substrates. As their substrates have important roles in many physiological processes, adequate function of calpains is mandatory for normal cellular functions. Read More

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http://dx.doi.org/10.1080/17460441.2020.1722638DOI Listing

Clinical and genetic characterization of limb girdle muscular dystrophy R7 telethonin-related patients from three unrelated Chinese families.

Neuromuscul Disord 2020 02 17;30(2):137-143. Epub 2019 Dec 17.

Department of Neurology and Institute of Neurology, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou, Fujian 350005, China; Fujian Key Laboratory of Molecular Neurology, Fuzhou, Fujian 350005, China. Electronic address:

Limb girdle muscular dystrophy LGMD R7 telethonin-related is a rare autosomal recessive muscle disorder characterized by proximal muscle weakness of pelvic and shoulder girdles. Mutation in TCAP is responsible for LGMD R7, and the disease has a wide geographic distribution in diverse populations, but genotype-phenotype relationships remain unclear. We collected 5 LGMD R7 patients from three unrelated Chinese families. Read More

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http://dx.doi.org/10.1016/j.nmd.2019.12.004DOI Listing
February 2020

A novel missense mutation in CAV3 gene in an Italian family with persistent hyperCKemia, myalgia and hypercholesterolemia: Double-trouble.

Clin Neurol Neurosurg 2020 Apr 23;191:105687. Epub 2020 Jan 23.

University of Campania "Luigi Vanvitelli", Italy.

Caveolins are essential proteins in caveolae architecture, small plasma membrane invaginations that play a key role in a variety of cellular processes, including vesicular trafficking and signal transduction. Mutations in the gene encoding caveolin-3 (CAV3) cause a broad spectrum of clinical phenotypes, ranging from isolated hyperCKemia to most severe limb girdle muscular dystrophy and cardiomyopathy. We report a novel heterozygous p. Read More

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http://dx.doi.org/10.1016/j.clineuro.2020.105687DOI Listing

hnRNPDL Phase Separation Is Regulated by Alternative Splicing and Disease-Causing Mutations Accelerate Its Aggregation.

Cell Rep 2020 Jan;30(4):1117-1128.e5

Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autónoma de Barcelona, Bellaterra 08193, Spain. Electronic address:

Prion-like proteins form multivalent assemblies and phase separate into membraneless organelles. Heterogeneous ribonucleoprotein D-like (hnRNPDL) is a RNA-processing prion-like protein with three alternative splicing (AS) isoforms, which lack none, one, or both of its two disordered domains. It has been suggested that AS might regulate the assembly properties of RNA-processing proteins by controlling the incorporation of multivalent disordered regions in the isoforms. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.12.080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996132PMC
January 2020

Calpainopathy: Description of a Novel Mutation and Clinical Presentation with Early Severe Contractures.

Genes (Basel) 2020 01 25;11(2). Epub 2020 Jan 25.

Grupo de Investigación en Psiquiatría (GIPSI), Departamento de Psiquiatría, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.

Presented here are five members of a family that was ascertained from an isolated, consanguineous, indigenous Amerindian community in Colombia that was affected with calpain 3-related, limb-girdle muscular dystrophy type R1. These patients are homozygous for a unique and novel deletion of four bases (TGCC) in exon 3 of the calpain 3 gene () (NM_000070.2; NP_000061. Read More

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http://dx.doi.org/10.3390/genes11020129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074289PMC
January 2020

Novel Recessive TNNT1 Congenital Core-Rod Myopathy in French Canadians.

Ann Neurol 2020 Apr 8;87(4):568-583. Epub 2020 Feb 8.

Department of Child Neurology, Centre Hospitalier de l'Université Laval et Centre Mère-Enfant Soleil, Université Laval, Quebec City, Quebec, Canada.

Objective: Recessive null variants of the slow skeletal muscle troponin T1 (TNNT1) gene are a rare cause of nemaline myopathy that is fatal in infancy due to respiratory insufficiency. Muscle biopsy shows rods and fiber type disproportion. We report on 4 French Canadians with a novel form of recessive congenital TNNT1 core-rod myopathy. Read More

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http://dx.doi.org/10.1002/ana.25685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078025PMC

The use of ivabradine in a patient with inappropriate sinus tachycardia and cardiomyopathy due to limb girdle muscular dystrophy type 2I.

BMJ Case Rep 2020 Jan 21;13(1). Epub 2020 Jan 21.

College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.

Muscular dystrophies are a heterogeneous group of disorders that commonly involve cardiac and skeletal muscle. Comprehensive guidelines for the management of cardiac failure and arrhythmias are available. However, the studies from which their recommendations are derived did not include any patients with muscular dystrophy. Read More

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http://dx.doi.org/10.1136/bcr-2019-230647DOI Listing
January 2020

Mutations in the J domain of DNAJB6 cause dominant distal myopathy.

Neuromuscul Disord 2020 01 19;30(1):38-46. Epub 2019 Nov 19.

Neuromuscular Research Center, Tampere University Hospital and Tampere University, P.O. box 100, FIN-33014 Tampere, Finland; Folkhälsan Research Center, Helsinki, Finland and University of Helsinki, Medicum, Helsinki, Finland.

Eight patients from five families with undiagnosed dominant distal myopathy underwent clinical, neurophysiological and muscle biopsy examinations. Molecular genetic studies were performed using targeted sequencing of all known myopathy genes followed by segregation of the identified mutations in the affected families using Sanger sequencing. Two novel mutations in DNAJB6 J domain, c. Read More

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http://dx.doi.org/10.1016/j.nmd.2019.11.005DOI Listing
January 2020
2.638 Impact Factor

The impact of exome sequencing on the diagnostic yield of muscular dystrophies in consanguineous families.

Eur J Med Genet 2020 Apr 15;63(4):103845. Epub 2020 Jan 15.

Department of Pathology and Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman, Jordan; Human and Molecular Genetics, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA. Electronic address:

Muscular dystrophies (MDs) are a heterogeneous group of inherited disorders that are characterized by progressive skeletal muscle weakness and dystrophic changes on muscle biopsy. The broad genetic and clinical heterogeneity of MDs make the accurate diagnosis difficult via conventional approaches. This study investigated 23 patients from eight unrelated consanguineous families with MDs. Read More

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http://dx.doi.org/10.1016/j.ejmg.2020.103845DOI Listing

Mutational spectrum of autosomal recessive limb-girdle muscular dystrophies in a cohort of 112 Iranian patients and reporting of a possible founder effect.

Orphanet J Rare Dis 2020 01 14;15(1):14. Epub 2020 Jan 14.

Dr. Zeinali's Medical Genetics Laboratory, Kawsar Human Genetics Research Center, Tehran, Iran.

Background: Limb-girdle muscular dystrophies are a group of genetically heterogeneous diseases that are inherited in both autosomal dominant (LGMDD) and autosomal recessive forms (LGMDR), the latter is more common especially in populations with high consanguineous marriages like Iran. In the present study, we aimed to investigate the genetic basis of patients who are suspicious of being affected by LGMDR. DNA samples of 60 families suspected of LGMD were extracted from their whole blood. Read More

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http://dx.doi.org/10.1186/s13023-020-1296-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961257PMC
January 2020

The Latin American experience with a next generation sequencing genetic panel for recessive limb-girdle muscular weakness and Pompe disease.

Orphanet J Rare Dis 2020 01 13;15(1):11. Epub 2020 Jan 13.

Sanofi Genzyme, Cambridge, MA, USA.

Background: Limb-girdle muscular dystrophy (LGMD) is a group of neuromuscular disorders of heterogeneous genetic etiology with more than 30 directly related genes. LGMD is characterized by progressive muscle weakness involving the shoulder and pelvic girdles. An important differential diagnosis among patients presenting with proximal muscle weakness (PMW) is late-onset Pompe disease (LOPD), a rare neuromuscular glycogen storage disorder, which often presents with early respiratory insufficiency in addition to PMW. Read More

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http://dx.doi.org/10.1186/s13023-019-1291-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958675PMC
January 2020

Cardiac Intervention Improves Heart Disease and Clinical Outcomes in Patients With Muscular Dystrophy in a Multidisciplinary Care Setting.

J Am Heart Assoc 2020 Jan 14;9(2):e014004. Epub 2020 Jan 14.

Division of Cardiology Faculty of Medicine and Dentistry University of Alberta Edmonton Canada.

Background Patients with muscular dystrophy (MD) represent a vulnerable patient population with no clearly defined care model in modern-day clinical practice to manage a high burden of heart disease and comorbidities. We demonstrate the effectiveness of cardiac interventions, namely the initiation and optimization of medical and device therapies, as part of a multidisciplinary care approach to improve clinical outcomes in patients with MD. Methods and Results We conducted a prospective cohort study at the Neuromuscular Multidisciplinary clinic following patients with dystrophinopathies, limb-girdle MD, type 1 myotonic dystrophy, and facioscapulohumeral MD. Read More

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http://dx.doi.org/10.1161/JAHA.119.014004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033817PMC
January 2020

A novel variant of contributes to merosin deficient congenital muscular dystrophy type 1A: Case report.

Biomed Rep 2020 Feb 27;12(2):46-50. Epub 2019 Nov 27.

Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec International Hospital, Hanoi 100000, Vietnam.

Merosin deficient congenital muscular dystrophy type 1A (MDC1A) is caused by defects in the gene. Patients with MDC1A exhibit severe symptoms, including congenital hypotonia, delayed motor development and contractures. The present case report describes a Vietnamese male child with clinical manifestations of delayed motor development, limb-girdle muscular dystrophy, severe scoliosis and white matter abnormality in the brain. Read More

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http://dx.doi.org/10.3892/br.2019.1260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6951223PMC
February 2020

POGLUT1 biallelic mutations cause myopathy with reduced satellite cells, α-dystroglycan hypoglycosylation and a distinctive radiological pattern.

Acta Neuropathol 2020 Mar 3;139(3):565-582. Epub 2020 Jan 3.

Neuromuscular Disorders Unit, Department of Neurology, Instituto de Biomedicina de Sevilla, Hospital U. Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.

Protein O-glucosyltransferase 1 (POGLUT1) activity is critical for the Notch signaling pathway, being one of the main enzymes responsible for the glycosylation of the extracellular domain of Notch receptors. A biallelic mutation in the POGLUT1 gene has been reported in one family as the cause of an adult-onset limb-girdle muscular dystrophy (LGMD R21; OMIM# 617232). As the result of a collaborative international effort, we have identified the first cohort of 15 patients with LGMD R21, from nine unrelated families coming from different countries, providing a reliable phenotype-genotype and mechanistic insight. Read More

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http://dx.doi.org/10.1007/s00401-019-02117-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196238PMC

Plasmid-Mediated Gene Therapy in Mouse Models of Limb Girdle Muscular Dystrophy.

Mol Ther Methods Clin Dev 2019 Dec 14;15:294-304. Epub 2019 Oct 14.

Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305-5120, USA.

We delivered plasmid DNA encoding therapeutic genes to the muscles of mouse models of limb girdle muscular dystrophy (LGMD) 2A, 2B, and 2D, deficient in calpain3, dysferlin, and alpha-sarcoglycan, respectively. We also delivered the human follistatin gene, which has the potential to increase therapeutic benefit. After intramuscular injection of DNA, electroporation was applied to enhance delivery to muscle fibers. Read More

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http://dx.doi.org/10.1016/j.omtm.2019.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923511PMC
December 2019

Defects in G-Actin Incorporation into Filaments in Myoblasts Derived from Dysferlinopathy Patients Are Restored by Dysferlin C2 Domains.

Int J Mol Sci 2019 Dec 19;21(1). Epub 2019 Dec 19.

Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile.

Dysferlin is a transmembrane C-2 domain-containing protein involved in vesicle trafficking and membrane remodeling in skeletal muscle cells. However, the mechanism by which dysferlin regulates these cellular processes remains unclear. Since actin dynamics is critical for vesicle trafficking and membrane remodeling, we studied the role of dysferlin in Ca-induced G-actin incorporation into filaments in four different immortalized myoblast cell lines (DYSF2, DYSF3, AB320, and ER) derived from patients harboring mutations in the gene. Read More

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http://dx.doi.org/10.3390/ijms21010037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981584PMC
December 2019

Obstetric management of a woman with limb-girdle muscular dystrophy type 2i and dilated cardiomyopathy.

Obstet Med 2019 Dec 11;12(4):199-201. Epub 2018 Dec 11.

Department of Obstetrics and Gynaecology, Western Sussex Hospitals NHS Foundation Trust, West Sussex, UK.

Limb-girdle muscular dystrophy describes a clinical phenotype with progressive weakness and atrophy of the muscles of the shoulders and hips. One of the more common types, limb-girdle muscular dystrophy type 2i, is associated with impaired cardiac function and restrictive lung disease, typically disproportionate to muscular disease. This condition presents a number of complex challenges in pregnancy and there are few case reports of its successful management. Read More

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http://dx.doi.org/10.1177/1753495X18814622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909294PMC
December 2019