3,386 results match your criteria Congenital Muscular Dystrophy


The common microRNA signatures associated with mitochondrial dysfunction in different muscular dystrophies.

Am J Pathol 2020 Jul 7. Epub 2020 Jul 7.

Department of Medical Biology, Hacettepe University Faculty of Medicine, 06100 Sihhiye, Ankara, Turkey. Electronic address:

Secondary mitochondrial damage in skeletal muscles is a common feature of different neuromuscular disorders (NMD), which fall outside the mitochondrial cytopathies. The common cause of mitochondrial dysfunction and structural changes in skeletal muscle tissue remains to be discovered. Although they are associated with different clinical, genetic, and pathological backgrounds, the pathomechanisms underlying NMDs might be attributed to the complex interaction and crosstalk between mitochondria and the associated microRNAs (miRNAs). Read More

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http://dx.doi.org/10.1016/j.ajpath.2020.06.011DOI Listing

Cervical Hyperextension Treated by Posterior Spinal Correction and Fusion in A Patient with Ullrich Congenital Muscular Dystrophy: A Case Report.

JBJS Case Connect 2020 Apr-Jun;10(2):e0392

1Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.

Case: An 18-year-old man with Ullrich congenital muscular dystrophy (UCMD) noted difficulty of looking forward and discomfort swallowing and breathing because of his hyperextended neck. We treated his cervical deformity with posterior spinal correction and fusion alone. He underwent a tracheotomy because of lung function deterioration 2 years after cervical surgery. Read More

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http://dx.doi.org/10.2106/JBJS.CC.19.00392DOI Listing

Circulating Biomarkers in Muscular Dystrophies: Disease and Therapy Monitoring.

Mol Ther Methods Clin Dev 2020 Sep 22;18:230-239. Epub 2020 May 22.

Department of Molecular Genetics, Function & Therapy, The Cyprus Institute of Neurology and Genetics, PO Box 23462, 1683 Nicosia, Cyprus.

Muscular dystrophies are a group of inherited disorders that primarily affect the muscle tissues. Across the muscular dystrophies, symptoms commonly compromise the quality of life in all areas of functioning. It is well noted that muscular dystrophies need reliable and measurable biomarkers that will monitor the progress of the disease and evaluate the potential therapeutic approaches. Read More

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http://dx.doi.org/10.1016/j.omtm.2020.05.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327849PMC
September 2020

Exon-Skipping Oligonucleotides Restore Functional Collagen VI by Correcting a Common COL6A1 Mutation in Ullrich CMD.

Mol Ther Nucleic Acids 2020 Jun 1;21:205-216. Epub 2020 Jun 1.

NIHR Great Ormond Street Hospital Biomedical Research Centre, London WC1N 1EH, UK; Genetics and Genomic Medicine Research and Teaching Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK. Electronic address:

Collagen VI-related congenital muscular dystrophies (COL6-CMDs) are the second most common form of congenital muscular dystrophy. Currently, there is no effective treatment available. COL6-CMDs are caused by recessive or dominant mutations in one of the three genes encoding for the α chains of collagen type VI (COL6A1, COL6A2, and COL6A3). Read More

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http://dx.doi.org/10.1016/j.omtn.2020.05.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321786PMC

Clinical spectrum and genetic variations of -related muscular dystrophies in a large cohort of Chinese patients.

J Med Genet 2020 Jun 22. Epub 2020 Jun 22.

Department of Pediatrics, Peking University First Hospital, Beijing, China

Background: -related muscular dystrophy is caused by mutations in gene. We aimed to identify genetic variations and clinical features in a large cohort of Chinese patients with mutations in an attempt to establish genotype-phenotype correlation.

Methods: The clinical presentations of patients with -related muscular dystrophy were recorded using retrospective and prospective cohort study. Read More

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http://dx.doi.org/10.1136/jmedgenet-2019-106671DOI Listing

[Clinical features and LAMA2 mutations of patients with congenital muscular dystrophy type 1A: a case report and literature review].

Zhongguo Dang Dai Er Ke Za Zhi 2020 Jun;22(6):608-613

Department of Pediatrics, First Affiliated Hospital, Jinan University, Guangzhou 510630, China.

Biallelic pathogenic mutations of the LAMA2 gene result in congenital muscular dystrophy type 1A (CMD1A). The patient in this study was a boy aged 19 months, with the clinical manifestations of motor development delay and increases in the serum levels of creatine kinase, aminotransferases, and lactate dehydrogenase. Genetic analysis showed that the patient had compound heterozygous mutations in the LAMA2 gene, among which c. Read More

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Impaired Regeneration in Dystrophic Muscle-New Target for Therapy.

Front Mol Neurosci 2020 25;13:69. Epub 2020 May 25.

Felsenstein Medical Research Center (FMRC), Tel-Aviv University, Tel-Aviv, Israel.

Muscle stem cells (MuSCs), known as satellite cells (SCs) have an incredible ability to regenerate, which enables the maintenance and growth of muscle tissue. In response to damaging stimuli, SCs are activated, proliferate, differentiate, and fuse to repair or generate a new muscle fiber. However, dystrophic muscles are characterized by poor muscle regeneration along with chronic inflammation and fibrosis. Read More

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http://dx.doi.org/10.3389/fnmol.2020.00069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261890PMC

First Clinical and Myopathological Description of a Myofibrillar Myopathy with Congenital Onset and Homozygous Mutation in FLNC.

Hum Mutat 2020 Jun 9. Epub 2020 Jun 9.

Department of Pediatric Neurology, Developmental Neurology and Social Pediatrics, University of Essen, Germany.

Filamin C (encoded by the FLNC gene) is a large actin-cross-linking protein involved in shaping the actin cytoskeleton in response to signaling events both at the sarcolemma and at myofibrillar Z-discs of cross-striated muscle cells. Multiple mutations in FLNC are associated with myofibrillar myopathies of autosomal dominant inheritance. Here, we describe for the first time a boy with congenital onset of generalized muscular hypotonia and muscular weakness, delayed motor development but no cardiac involvement associated with a homozygous FLNC mutation c. Read More

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http://dx.doi.org/10.1002/humu.24062DOI Listing
June 2020
5.144 Impact Factor

Assessing Motor Function in Congenital Muscular Dystrophy Patients Using Accelerometry.

J Neurosci Nurs 2020 Aug;52(4):172-178

Joshua J. Todd, PhD, is Research Fellow, National Institute of Nursing Research, NIH, Bethesda, MD. Jeffrey S. Elliott, BS, is Post-Baccalaureate Fellow, National Institute of Nursing Research, NIH, Bethesda, MD. Melody M. Linton, BS, is Post-Baccalaureate Fellow, National Institute of Nursing Research, NIH, Bethesda, MD. Megan Andres, BS, is Post-Baccalaureate Fellow, National Institute of Nursing Research, NIH, Bethesda, MD. Jessica W. Witherspoon, DPT, PhD, is Research Fellow, National Institute of Nursing Research, NIH, Bethesda, MD. John P. Collins, MD, PhD, is Assistant Professor, Mark O. Hatfield Clinical Research Center, NIH, Bethesda, MD; and Department of Rehabilitation Science, George Mason University, Fairfax, VA. Irene C. Chrismer, BSN, is Research Nurse, National Institute of Nursing Research, NIH, Bethesda, MD. Fatoumata Tounkara, PhD, is Post-Baccalaureate Fellow, National Institute of Nursing Research, NIH, Bethesda, MD. Melissa R. Waite, MSPT, is Physical Therapist, Mark O. Hatfield Clinical Research Center, NIH, Bethesda, MD. Carmel Nichols, BA, is Post-Baccalaureate Fellow, Mark O. Hatfield Clinical Research Center, NIH, Bethesda, MD. Carsten G. Bönnemann, MD, is Neurologist, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD. Carole Vuillerot, MD, PhD, is Pediatrician, Service de Médecine Physique et de Réadaptation Pédiatrique, Hôpital Femme-Mère-Enfant, Hospices Civils de Lyon, Bron, France. Roxanna Bendixen, PhD, is Associate Professor, Department of Occupational Therapy, University of Pittsburgh, Pittsburgh, PA. Minal S. Jain, DSc, is Physical Therapist, Mark O. Hatfield Clinical Research Center, NIH, Bethesda, MD. Katherine G. Meilleur, PhD, is Pediatric Nurse Practitioner, National Institute of Nursing Research, NIH, Bethesda, MD.

Background: When tested in a controlled clinic environment, individuals with neuromuscular-related symptoms may complete motor tasks within normal predicted ranges. However, measuring activity at home may better reflect typical motor performance. The accuracy of accelerometry measurements in individuals with congenital muscular dystrophy (CMD) is unknown. Read More

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http://dx.doi.org/10.1097/JNN.0000000000000519DOI Listing

Novel variants identified in a patient with white matter abnormalities.

Hum Genome Var 2020 26;7:16. Epub 2020 May 26.

Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.

Comprehensive genomic analysis was performed in a patient with mild psychomotor developmental delay, elevated creatine kinase, and white matter abnormalities. The results revealed biallelic pathogenic variants in the gene related to merosin-deficient congenital muscular dystrophy, NM_000426.3(LAMA2):c. Read More

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http://dx.doi.org/10.1038/s41439-020-0103-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248065PMC

Human laminin-111 and laminin-211 protein therapy prevents muscle disease progression in an immunodeficient mouse model of LAMA2-CMD.

Skelet Muscle 2020 Jun 4;10(1):18. Epub 2020 Jun 4.

Department of Pharmacology, University of Nevada, Reno School of Medicine, Reno, NV, 89557, USA.

Background: Laminin-α2-related congenital muscular dystrophy (LAMA2-CMD) is a devastating genetic disease caused by mutations in the LAMA2 gene. These mutations result in progressive muscle wasting and inflammation leading to delayed milestones, and reduced lifespan in affected patients. There is currently no cure or treatment for LAMA2-CMD. Read More

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http://dx.doi.org/10.1186/s13395-020-00235-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271547PMC

Reporting one very rare pathogenic variation c.1106G>A in gene.

Intractable Rare Dis Res 2020 May;9(2):104-108

Genetic Counseling Center, Shiraz Welfare Organization, Shiraz, Iran.

Dystroglycan (DG) is a major cell membrane glycoprotein, which is encoded by the gene. α-DG is one of DG subunits, belongs to O-mannosylated protein of mammals and was identified in brain, peripheral nerves and muscle. Dystroglycanopathies are a group of heterogeneous congenital muscular dystrophies, which can result from defective α-DG mannosylation. Read More

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http://dx.doi.org/10.5582/irdr.2020.03013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263986PMC

Laminin-111 protein therapy after disease onset slows muscle disease in a mouse model of Laminin-α2 related congenital muscular dystrophy.

Hum Mol Genet 2020 May 29. Epub 2020 May 29.

Department of Pharmacology, University of Nevada, Reno School of Medicine, Reno, NV 89557, USA.

Laminin-α2 related Congenital Muscular Dystrophy (LAMA2-CMD) is a fatal muscle disease caused by mutations in the LAMA2 gene. Laminin-α2 is critical for the formation of Laminin-211 and -221 heterotrimers in the muscle basal lamina. LAMA2-CMD patients exhibit hypotonia from birth and progressive muscle loss that results in developmental delay, confinement to a wheelchair, respiratory insufficiency and premature death. Read More

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http://dx.doi.org/10.1093/hmg/ddaa104DOI Listing

A Family of Laminin α2 Chain-Deficient Mouse Mutants: Advancing the Research on LAMA2-CMD.

Front Mol Neurosci 2020 21;13:59. Epub 2020 Apr 21.

Muscle Biology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.

The research on laminin α2 chain-deficient congenital muscular dystrophy (LAMA2-CMD) advanced rapidly in the last few decades, largely due to availability of good mouse models for the disease and a strong interest in preclinical studies from scientists all over the world. These mouse models continue to provide a solid platform for understanding the LAMA2-CMD pathology. In addition, they enable researchers to test laborious, necessary routines, but also the most creative scientific approaches in order to design therapy for this devastating disorder. Read More

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http://dx.doi.org/10.3389/fnmol.2020.00059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188397PMC

Consequences of Exon 4 Mutations in Myoblast Function.

Cells 2020 May 21;9(5). Epub 2020 May 21.

Instituto de Investigación de Enfermedades Raras, Instituto de Salud Carlos III, Ctra. Majadahonda-Pozuelo km2.2, E-28029 Madrid, Spain.

Laminopathies are causally associated with mutations on the Lamin A/C gene (). To date, more than 400 mutations in have been reported in patients. These mutations are widely distributed throughout the entire gene and are associated with a wide range of phenotypes. Read More

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http://dx.doi.org/10.3390/cells9051286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291140PMC

Congenital hearing impairment associated with peripheral cochlear nerve dysmyelination in glycosylation-deficient muscular dystrophy.

PLoS Genet 2020 May 26;16(5):e1008826. Epub 2020 May 26.

Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University, Kobe, Japan.

Hearing loss (HL) is one of the most common sensory impairments and etiologically and genetically heterogeneous disorders in humans. Muscular dystrophies (MDs) are neuromuscular disorders characterized by progressive degeneration of skeletal muscle accompanied by non-muscular symptoms. Aberrant glycosylation of α-dystroglycan causes at least eighteen subtypes of MD, now categorized as MD-dystroglycanopathy (MD-DG), with a wide spectrum of non-muscular symptoms. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274486PMC

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

Neuromuscul Disord 2020 Jun 18;30(6):483-491. 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

Clinical and genomic characteristics of LAMA2 related congenital muscular dystrophy in a patients' cohort from Qatar. A population specific founder variant.

Neuromuscul Disord 2020 Jun 17;30(6):457-471. Epub 2020 Apr 17.

Department of Adult Neurology, Hamad Medical Corporation, Doha, Qatar.

Congenital LAMA2 related muscular dystrophy (LAMA2-RD), the most commonly recognized type of congenital muscular dystrophies, has been described in patients' cohorts from Europe and the UK but not from Middle-Eastern. This study aimed to reveal the prevalence, clinical and genomic characteristics of congenital LAMA2-RD in a patient's cohort of 17 families (21 patients) from the Gulf and Middle East. Affected subjects exhibited the classic phenotype of generalized hypotonia, developmental delay, and progressive muscular weakness. Read More

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http://dx.doi.org/10.1016/j.nmd.2020.03.009DOI Listing

New MRI Findings in Fukuyama Congenital Muscular Dystrophy: Brain Stem and Venous System Anomalies.

AJNR Am J Neuroradiol 2020 Jun 21;41(6):1094-1098. Epub 2020 May 21.

From the Departments of Child Neurology (A.H.-I., A.I., E.T., H.K., M.S.).

Background And Purpose: Leptomeningeal glioneuronal heterotopia of the brain stem and cerebral migration abnormality were pathologically reported in Fukuyama congenital muscular dystrophy, but the radiologic assessments of the brain stem and cerebral venous system (which may be involved in the development of the anomaly) were insufficient. Here, we evaluated the brain stem and cerebral veins on MR imaging in patients with Fukuyama congenital muscular dystrophy.

Materials And Methods: We retrospectively reviewed the MR imaging findings of 27 patients with Fukuyama congenital muscular dystrophy. Read More

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http://dx.doi.org/10.3174/ajnr.A6577DOI Listing

Pathogenic variants in COL6A3 cause Ullrich-like congenital muscular dystrophy in young Labrador Retriever dogs.

Neuromuscul Disord 2020 May 16;30(5):360-367. Epub 2020 Apr 16.

Department of Pathology, School of Medicine, University of California San Diego, La Jolla, CA 92093-0709, USA. Electronic address:

The collagen VI-related muscular dystrophies in people include a broad spectrum of diseases ranging from the severe Ullrich congenital muscular dystrophy to the mild Bethlem myopathy. Clinical features are attributable to both muscle and connective tissue and include progressive muscle weakness and respiratory failure, hyperlaxity of distal joints, and progressive contracture of large joints. Here we describe two different COL6A3 pathogenic variants in Labrador Retriever dogs that result in autosomal recessive or autosomal dominant congenital myopathies with hyperlaxity of distal joints and joint contracture, similar to the condition in people. Read More

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http://dx.doi.org/10.1016/j.nmd.2020.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292757PMC

Towards stem cell therapies for skeletal muscle repair.

NPJ Regen Med 2020 11;5:10. Epub 2020 May 11.

2Biomedical Research Centre, Department of Medical Genetics, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC Canada.

Skeletal muscle is an ideal target for cell therapy. The use of its potent stem cell population in the form of autologous intramuscular transplantation represents a tantalizing strategy to slow the progression of congenital muscle diseases (such as Duchenne Muscular Dystrophy) or regenerate injured tissue following trauma. The syncytial nature of skeletal muscle uniquely permits the engraftment of stem/progenitor cells to contribute to new myonuclei and restore the expression of genes mutated in myopathies. Read More

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http://dx.doi.org/10.1038/s41536-020-0094-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214464PMC

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

Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain.

Genes (Basel) 2020 05 11;11(5). Epub 2020 May 11.

Genetics Department Hospital de Sant Pau, IIB Sant Pau, 08041 Barcelona, Spain.

The term neuromuscular disorder (NMD) includes many genetic and acquired diseases and differential diagnosis can be challenging. Next-generation sequencing (NGS) is especially useful in this setting given the large number of possible candidate genes, the clinical, pathological, and genetic heterogeneity, the absence of an established genotype-phenotype correlation, and the exceptionally large size of some causative genes such as , and We evaluated the diagnostic value of a custom targeted next-generation sequencing gene panel to study the mutational spectrum of a subset of NMD patients in Spain. In an NMD cohort of 207 patients with congenital myopathies, distal myopathies, congenital and adult-onset muscular dystrophies, and congenital myasthenic syndromes, we detected causative mutations in 102 patients (49. Read More

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http://dx.doi.org/10.3390/genes11050539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288461PMC

GGPS1 Mutations Cause Muscular Dystrophy/Hearing Loss/Ovarian Insufficiency Syndrome.

Ann Neurol 2020 May 13. Epub 2020 May 13.

Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.

Objective: A hitherto undescribed phenotype of early onset muscular dystrophy associated with sensorineural hearing loss and primary ovarian insufficiency was initially identified in 2 siblings and in subsequent patients with a similar constellation of findings. The goal of this study was to understand the genetic and molecular etiology of this condition.

Methods: We applied whole exome sequencing (WES) superimposed on shared haplotype regions to identify the initial biallelic variants in GGPS1 followed by GGPS1 Sanger sequencing or WES in 5 additional families with the same phenotype. Read More

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http://dx.doi.org/10.1002/ana.25772DOI Listing

LAMA2 Neuropathies: Human Findings and Pathomechanisms From Mouse Models.

Front Mol Neurosci 2020 23;13:60. Epub 2020 Apr 23.

Department of Neurology, IRCCS Ospedale San Raffaele, Milan, Italy.

Merosin deficient Congenital Muscular Dystrophy (MDC1A), or LAMA2-related muscular dystrophy (LAMA2-RD), is a recessive disorder resulting from mutations in the gene, encoding for the alpha-2 chain of laminin-211. The disease is predominantly characterized by progressive muscular dystrophy affecting patient motor function and reducing life expectancy. However, LAMA2-RD also comprises a developmentally-associated dysmyelinating neuropathy that contributes to the disease progression, in addition to brain abnormalities; the latter often underappreciated. Read More

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http://dx.doi.org/10.3389/fnmol.2020.00060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190814PMC

Successful treatment of intractable epilepsy with ketogenic diet therapy in twins with ALG3-CDG.

Brain Dev 2020 Aug 7;42(7):539-545. Epub 2020 May 7.

Department of Paediatric Neurology, School of Medicine, Dokuz Eylul University, Izmir, Turkey.

Background: Congenital disorders of glycosylation (CDG) is a heterogeneous group of congenital metabolic diseases with multisystem clinical involvement. ALG3-CDG is a very rare subtype with only 24 cases reported so far.

Case: Here, we report two siblings with dysmorphic features, growth retardation, microcephaly, intractable epilepsy, and hemangioma in the frontal, occipital and lumbosacral regions. Read More

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http://dx.doi.org/10.1016/j.braindev.2020.04.008DOI Listing

Multisystemic Impairments in 93 Chinese Patients With Myotonic Dystrophy Type 1.

Front Neurol 2020 21;11:277. Epub 2020 Apr 21.

Department of Neurology of the First Medical Center, Chinese PLA General Hospital, Beijing, China.

Myotonic dystrophy type 1 (DM1) is an autosomal dominant neuromuscular disease characterized by muscle weakness and multisystemic impairments, which significantly impact the quality of life. There is currently an increasing consensus on the necessity of a multidisciplinary assessment in patients with DM1, to improve the management of the disease. To analyze the prevalence and pairwise relationships between various organs involved, we performed a retrospective study by reviewing demographic and clinical information of DM1 patients including age, disease duration, clinical history, muscular impairment rating scale score (MIRS), results of blood biochemistry, electrocardiogram, echocardiography, and ophthalmologic examination. Read More

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http://dx.doi.org/10.3389/fneur.2020.00277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186325PMC

Non-traumatic and non-drug-induced rhabdomyolysis.

Arch Med Sci Atheroscler Dis 2019 2;4:e252-e263. Epub 2019 Dec 2.

Cardiology Department, Onassis Cardiac Surgery Center, Athens, Greece.

Rhabdomyolysis (RM), a fortunately rare disease of the striated muscle cells, is a complication of non-traumatic (congenital (glycogen storage disease, discrete mitochondrial myopathies and various muscular dystrophies) or acquired (alcoholic myopathy, systemic diseases, arterial occlusion, viral illness or bacterial sepsis)) and traumatic conditions. Additionally, RM can occur in some individuals under specific circumstances such as toxic substance use and illicit drug abuse. Lipid-lowering drugs in particular are capable of causing RM. Read More

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http://dx.doi.org/10.5114/amsad.2019.90152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191942PMC
December 2019

Severe congenital myasthenic syndrome associated with novel biallelic mutation of the CHRND gene.

Neuromuscul Disord 2020 Apr 24;30(4):336-339. Epub 2020 Feb 24.

Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg, Germany; Centro Nacional de Análisis Genómico (CNAG-CRG), Center for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Catalonia, Spain; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada; Department of Medicine, Division of Neurology, The Ottawa Hospital, Ottawa, Canada.

Congenital myasthenic syndromes (CMS) are a group of inherited disorders caused by mutations in genes encoding proteins essential for neuromuscular transmission. CMS is characterized by fatigable muscle weakness with onset at birth or in early childhood; rarely, symptoms may present later. The most frequently involved proteins are choline acetyltransferase, the endplate species of acetylcholinesterase and the acetylcholine receptor subunits. Read More

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http://dx.doi.org/10.1016/j.nmd.2020.02.012DOI Listing

Identification and Modeling of a GT-A Fold in the α-Dystroglycan Glycosylating Enzyme LARGE1.

J Chem Inf Model 2020 Jun 14;60(6):3145-3156. Epub 2020 May 14.

Institute of Chemical Sciences and Technologies "Giulio Natta" (SCITEC)-CNR, L.go F. Vito 1, 00168 Rome, Italy.

The acetylglucosaminyltransferase-like protein LARGE1 is an enzyme that is responsible for the final steps of the post-translational modifications of dystroglycan (DG), a membrane receptor that links the cytoskeleton with the extracellular matrix in the skeletal muscle and in a variety of other tissues. LARGE1 acts by adding the repeating disaccharide unit [-3Xyl-α1,3GlcAβ1-] to the extracellular portion of the DG complex (α-DG); defects in the gene result in an aberrant glycosylation of α-DG and consequent impairment of its binding to laminin, eventually affecting the connection between the cell and the extracellular environment. In the skeletal muscle, this leads to degeneration of the muscular tissue and muscular dystrophy. Read More

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http://dx.doi.org/10.1021/acs.jcim.0c00281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340341PMC

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

Ann Clin Transl Neurol 2020 05 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

Clinical utility of multigene analysis in over 25,000 patients with neuromuscular disorders.

Neurol Genet 2020 Apr 9;6(2):e412. Epub 2020 Mar 9.

Invitae Corporation (T.L.W., C.A.T., S.K., H.W., J.M.W., J.Z.W., A.E., R.T., R.L.N., S.A.), San Francisco, CA; Volunteer Faculty (R.L.N.), University of California, San Francisco; and Center for Genetic Medicine (E.M.M.), Northwestern University, Evanston, IL.

Objective: Molecular genetic testing for hereditary neuromuscular disorders is increasingly used to identify disease subtypes, determine prevalence, and inform management and prognosis, and although many small disease-specific studies have demonstrated the utility of genetic testing, comprehensive data sets are better positioned to assess the complexity of genetic analysis.

Methods: Using high depth-of-coverage next-generation sequencing (NGS) with simultaneous detection of sequence variants and copy number variants (CNVs), we tested 25,356 unrelated individuals for subsets of 266 genes.

Results: A definitive molecular diagnosis was obtained in 20% of this cohort, with yields ranging from 4% among individuals with congenital myasthenic syndrome to 33% among those with a muscular dystrophy. Read More

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http://dx.doi.org/10.1212/NXG.0000000000000412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164976PMC

Melanocortin-1 receptor (MC1R) genotypes do not correlate with size in two cohorts of medium-to-giant congenital melanocytic nevi.

Pigment Cell Melanoma Res 2020 Apr 23. Epub 2020 Apr 23.

Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain.

Congenital melanocytic nevi (CMN) are cutaneous malformations whose prevalence is inversely correlated with projected adult size. CMN are caused by somatic mutations, but epidemiological studies suggest that germline genetic factors may influence CMN development. In CMN patients from the U. Read More

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http://dx.doi.org/10.1111/pcmr.12883DOI Listing

Preference-based measures of health-related quality of life in congenital mobility impairment: a systematic review of validity and responsiveness.

Health Econ Rev 2020 Apr 21;10(1). Epub 2020 Apr 21.

School of Health Sciences, Fron Heulog, Bangor University, Gwynedd, LL57 2EF, Wales, UK.

Introduction: Mobility impairment is the leading cause of disability in the UK. Individuals with congenital mobility impairments have unique experiences of health, quality of life and adaptation. Preference-based outcomes measures are often used to help inform decisions about healthcare funding and prioritisation, however the applicability and accuracy of these measures in the context of congenital mobility impairment is unclear. Read More

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http://dx.doi.org/10.1186/s13561-020-00270-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175543PMC

FAM3B/PANDER-Like Carbohydrate-Binding Domain in a Glycosyltransferase, POMGNT1.

Methods Mol Biol 2020 ;2132:609-619

Molecular Glycobiology, Research Team for Mechanism of Aging, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Itabashi-ku, Tokyo, Japan.

Protein O-mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) is one of the gene products responsible for α-dystroglycanopathy, which is a type of congenital muscular dystrophy caused by O-mannosyl glycan defects. The originally identified function of POMGNT1 was as a glycosyltransferase that catalyzes the formation of the GlcNAcβ1-2Man linkage of O-mannosyl glycan, but the enzyme function is not essential for α-dystroglycanopathy pathogenesis. Our recent study revealed that the stem domain of POMGNT1 has a carbohydrate-binding ability, which recognizes the GalNAcβ1-3GlcNAc structure. Read More

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http://dx.doi.org/10.1007/978-1-0716-0430-4_52DOI Listing
January 2020

Targeted Treatments for Inherited Neuromuscular Diseases of Childhood.

Semin Neurol 2020 Jun 15;40(3):335-341. Epub 2020 Apr 15.

Department of Neurology, University of California San Francisco, San Francisco, California.

In the past decade, the number of genes linked to neuromuscular diseases of childhood has expanded dramatically, and this genetic information is forming the basis for gene-specific and even mutation-specific therapies. At the forefront of these advances are the two recently approved treatments for spinal muscular atrophy: one, an antisense oligonucleotide that modifies splicing of the SMN2 gene, and, the other, a gene therapy vector that delivers the gene to motor neurons, both of which are allowing patients to acquire developmental milestones previously unseen in this fatal disease. This review highlights these advances and emerging targeted therapies for Duchenne muscular dystrophy and centronuclear myopathy, while also covering enzyme replacement therapy and small molecule-based targeted therapies for conditions such as Pompe's disease and congenital myasthenic syndromes. Read More

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http://dx.doi.org/10.1055/s-0040-1702940DOI Listing

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

Dropped head related lamin A/C associated congenital muscular dystrophy case; previously defined as emerydreifuss muscular dystrophy.

Turk J Pediatr 2020 ;62(1):130-135

Division of Child Neurology, Department of Pediatrics, Ege University Faculty of Medicine, İzmir, Turkey.

Dropped head syndrome can be seen in many neuromuscular diseases. However, there are very few diseases in which neck extensors are weak among neuromuscular diseases. A 7 years old boy who had weakness of the neck extensor muscles, creatinine kinase elevation and dystrophy findings in biopsy followed up with the preliminary diagnosis of muscular dystrophy is presented. Read More

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http://dx.doi.org/10.24953/turkjped.2020.01.019DOI Listing
January 2020

Lamin A/C Assembly Defects in -Congenital Muscular Dystrophy Is Responsible for the Increased Severity of the Disease Compared with Emery-Dreifuss Muscular Dystrophy.

Cells 2020 Mar 31;9(4). Epub 2020 Mar 31.

Institut de Myologie, Centre de Recherche en Myologie, Sorbonne Université, INSERM UMRS974, F-75651 Paris CEDEX 13, France.

encodes for Lamin A/C, type V intermediate filaments that polymerize under the inner nuclear membrane to form the nuclear lamina. A small fraction of Lamin A/C, less polymerized, is also found in the nucleoplasm. Lamin A/C functions include roles in nuclear resistance to mechanical stress and gene regulation. Read More

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http://dx.doi.org/10.3390/cells9040844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226786PMC

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

Lamin Mutations Cause Increased YAP Nuclear Entry in Muscle Stem Cells.

Cells 2020 Mar 27;9(4). Epub 2020 Mar 27.

INSERM UMRS_974, Centre for Research in Myology, Sorbonne Université, 75013 Paris, France.

Mutations in the gene, encoding the nuclear envelope A-type lamins, are responsible for muscular dystrophies, the most severe form being the -related congenital muscular dystrophy (L-CMD), with severe defects in myonucleus integrity. We previously reported that L-CMD mutations compromise the ability of muscle stem cells to modulate the yes-associated protein (YAP), a pivotal factor in mechanotransduction and myogenesis. Here, we investigated the intrinsic mechanisms by which lamins influence YAP subcellular distribution, by analyzing different conditions affecting the balance between nuclear import and export of YAP. Read More

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http://dx.doi.org/10.3390/cells9040816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226749PMC

Antioxidants Reduce Muscular Dystrophy in the Mouse Model of Laminin α2 Chain-Deficient Muscular Dystrophy.

Antioxidants (Basel) 2020 Mar 18;9(3). Epub 2020 Mar 18.

Unit of Muscle Biology, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden.

Congenital muscular dystrophy with laminin α2 chain-deficiency (LAMA2-CMD) is a severe neuromuscular disorder without a cure. Using transcriptome and proteome profiling as well as functional assays, we previously demonstrated significant metabolic impairment in skeletal muscle from LAMA2-CMD patients and mouse models. Reactive oxygen species (ROS) increase when oxygen homeostasis is not maintained and, here, we investigate whether oxidative stress indeed is involved in the pathogenesis of LAMA2-CMD. Read More

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http://dx.doi.org/10.3390/antiox9030244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139799PMC

Impact of gene therapy for canine monogenic diseases on the progress of preclinical studies.

Authors:
Marek Switonski

J Appl Genet 2020 May 18;61(2):179-186. Epub 2020 Mar 18.

Department of Genetics and Animal Breeding, Poznan University of Life Sciences, Poznan, Poland.

Rapid progress in knowledge of the organization of the dog genome has facilitated the identification of the mutations responsible for numerous monogenic diseases, which usually present a breed-specific distribution. The majority of these diseases have clinical and molecular counterparts in humans. The affected dogs have thus become valuable models for preclinical studies of gene therapy for problems such as eye diseases, immunodeficiency, lysosomal storage diseases, hemophilia, and muscular dystrophy. Read More

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http://dx.doi.org/10.1007/s13353-020-00554-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148265PMC

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 short form of gross motor function measure for Fukuyama congenital muscular dystrophy.

Brain Dev 2020 May 4;42(5):383-388. Epub 2020 Mar 4.

Department of Pediatrics, Tokyo Women's Medical University, School of Medicine, 8-1 Kawadacho, Shinjuku-ku, Tokyo 162-8666, Japan. Electronic address:

Objectives: The objective of this study was to confirm the validity of a short form of gross motor function measure for Fukuyama congenital muscular dystrophy (GMFM for FCMD).

Methods: This study is a case series and was conducted at the Tokyo Women's Medical University. Fifteen patients with FCMD were assessed using both the GMFM for FCMD with 68 items, which was created as a motor function measure for patients with FCMD on the basis of Rasch analysis, and the original GMFM with 88 items. Read More

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http://dx.doi.org/10.1016/j.braindev.2020.02.006DOI Listing

Risk factors for bronchiolitis hospitalization in infants: A French nationwide retrospective cohort study over four consecutive seasons (2009-2013).

PLoS One 2020 6;15(3):e0229766. Epub 2020 Mar 6.

Translational Health Economics Network (THEN), Paris, France.

Objectives: Large studies are needed to update risk factors of bronchiolitis hospitalization. We performed a nationwide analysis of hospitalization rates for bronchiolitis over four consecutive bronchiolitis seasons to identify underlying medical disorders at risk of bronchiolitis hospitalization and assess their frequency.

Methods: Data were retrieved from the French National Hospital Discharge database. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229766PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059917PMC

Total Hip Arthroplasty for High Hip Dislocation.

Z Orthop Unfall 2020 Apr 4;158(2):170-183. Epub 2020 Mar 4.

Musculoskeletal Surgery Centre, Charité - University Medicine Berlin.

Introduction: Total hip arthroplasty in patients with high hip dislocation is a surgically demanding procedure. This is due to the congenital disorder of hip maturation and the resulting anatomical features. The aim of the arthroplasty is implantation of the cup prosthesis in the original centre of rotation, at the same time correcting femoral deformities and reducing the hip joint. Read More

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http://dx.doi.org/10.1055/a-0946-2750DOI Listing

Walking and weakness in children: a narrative review of gait and functional ambulation in paediatric neuromuscular disease.

J Foot Ankle Res 2020 Mar 2;13(1):10. Epub 2020 Mar 2.

Department of Physiotherapy, The University of Melbourne, Parkville, Vic, Australia.

Background: Weakness is the primary impairment in paediatric neuromuscular diseases, impacting gait and gait-related functional activities in ambulant children affected by these rare and often degenerative diseases. Gait speed is an indicator of health and disability, yet gait is a complex, multi-faceted activity. Using the International Classification of Function, Health and Disability (ICF) model, assessment of gait and functional ambulation should consider the impairments, activity limitations and participation restrictions due to disease, and factors related to the environment and the individual person. Read More

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http://dx.doi.org/10.1186/s13047-020-0378-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052968PMC