3,268 results match your criteria: "Limb-Girdle Muscular Dystrophy"

Case report: A single novel calpain 3 gene variant associated with mild myopathy.

Front Genet

December 2024

Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genova, Italy.

Recessively inherited limb-girdle muscular dystrophy type 1, caused by mutations in the calpain 3 gene, is the most common limb-girdle muscular dystrophy worldwide. Recently, cases of autosomal dominant calpainopathy have been described. A man was referred to our neurological outpatient clinic at the age of 54 for persistent hyperCKemia (>1000 U/l) associated with muscle fatigue and myalgia.

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Development of differential diagnostic models for distinguishing between limb-girdle muscular dystrophy and idiopathic inflammatory myopathy.

Arthritis Res Ther

December 2024

Department of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Diseases, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China.

Objective: Limb-girdle muscular dystrophy (LGMD) is usually confused with idiopathic inflammatory myopathy (IIM) in clinical practice. Our study aimed to establish convenient and reliable diagnostic models for distinguishing between LGMD and IIM.

Methods: A total of 71 IIM patients, 24 LGMDR2 patients and 22 LGMDR1 patients diagnosed at our neuromuscular center were enrolled.

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Article Synopsis
  • Hereditary myopathies involve several hundred genetic variants, with Limb-girdle muscular dystrophies (LGMDs) being a diverse group of disorders linked to more than 30 genes, characterized primarily by limb weakness.
  • The study analyzed 2,372 patients across 21 countries to assess the prevalence of LGMD and Pompe disease through next-generation sequencing (NGS), finding that 11% had pathogenic genetic variants, with a high diagnostic effectiveness for LGMD (86.2%).
  • The findings emphasize the importance of including specific genes in NGS panels for diagnosing LGMW, contributing to a better understanding of LGMD and aiding in the identification of late-onset Pompe disease.
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Objective: Limb-girdle muscular dystrophy R9 (LGMDR9, formerly known as LGMD2I), caused by variants in the fukutin-related protein (FKRP) gene leads to progressive muscle weakness of the shoulder and pelvic limb-girdles and loss of motor function over time. Clinical management and future trial design are improved by determining which standardized clinical outcome assessments (COA) of function are most appropriate to capture disease presentation and progression, informing endpoint selection and enrollment criteria. The purpose of our study was to evaluate the cross-sectional validity and reliability of clinical outcome assessments in patients with FKRP-related LGMDR9 participating in the Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP) natural history study.

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Diagnosing missed cases of spinal muscular atrophy in genome, exome, and panel sequencing datasets.

Genet Med

December 2024

Program in Medical and Population Genetics, Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

Purpose: We set out to develop a publicly available tool that could accurately diagnose spinal muscular atrophy (SMA) in exome, genome or panel sequencing datasets aligned to a GRCh37, GRCh38, or T2T reference genome.

Methods: The SMA Finder algorithm detects the most common genetic causes of SMA by evaluating reads that overlap the c.840 position of the SMN1 and SMN2 paralogs.

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"Natural history of skeletal muscle laminopathies: a 2-year prospective study".

Neuromuscul Disord

November 2024

Neuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. Electronic address:

Article Synopsis
  • Skeletal muscle laminopathies (SMLs) are rare genetic disorders linked to mutations in the LMNA gene, affecting skeletal muscles.
  • A 2-year study involving 26 patients aimed to understand the progression of SMLs, using various assessments for muscle performance and respiratory function.
  • Results indicated a significant decline in muscle function (NSAA score) and respiratory capacity (FVC and FEV1) over two years, while other measurements like walking tests and joint flexibility remained stable.
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Mutations in protein -glucosyltransferase 1 ( ) cause a recessive form of limb-girdle muscular dystrophy (LGMD-R21) associated with reduced satellite cell number and NOTCH1 signaling in adult patient muscles and impaired myogenic capacity of patient-derived muscle progenitors. However, the roles of POGLUT1 in the development, function, and maintenance of satellite cells are not well understood. Here, we show that conditional deletion of mouse in myogenic progenitors leads to early lethality, postnatal muscle growth defects, reduced expression, abnormality in muscle extracellular matrix, and impaired muscle repair.

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Limb-girdle muscular dystrophies (LGMD) constitute a heterogeneous group of genetic disorders characterized by progressive muscle weakness and atrophy, predominantly affecting the muscles of the pelvic and shoulder girdles. LGMD R27, linked to biallelic pathogenic variants in the gene, was recently described, and to date, only 27 cases has been published in three reports. Here, we present two siblings exhibiting a severe clinical phenotype of LGMD R27, associated with a novel homozygous frameshift variant [c.

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Article Synopsis
  • FSHD is a muscle-wasting disease caused by the misexpression of the DUX4 transcription factor, leading to progressive muscle weakness starting from facial and shoulder muscles and eventually affecting the lower limbs.
  • The study utilized siRNAs to investigate the role of SIX family transcription factors in regulating DUX4 expression in patient-derived FSHD muscle cells, revealing that SIX1, SIX2, and SIX4 are essential for DUX4 induction during muscle differentiation.
  • Additionally, the research indicated that DUX4 actually downregulates SIX RNA levels, suggesting a negative feedback loop in the regulation of these transcription factors in FSHD contexts.
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Article Synopsis
  • Genetic neuromuscular disorders significantly impact muscle function and present challenges during pregnancy, necessitating a review of related obstetric outcomes.
  • A systematic analysis of 28 studies revealed common complications such as polyhydramnios, preterm labor, and increased rates of cesarean sections among pregnant women with disorders like myotonic dystrophy and spinal muscular atrophy.
  • Effective management of these high-risk pregnancies requires collaboration between neurologists and obstetricians, alongside further research to establish standardized care protocols.
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Hereditary Neuromuscular Disorders in Reproductive Medicine.

Genes (Basel)

October 2024

Unit of Medical Genetics and Genomics, San Bortolo Hospital, ULSS n.8 "Berica", 36100 Vicenza, Italy.

Neuromuscular disorders (NMDs) encompass a broad range of hereditary and acquired conditions that affect motor units, significantly impacting patients' quality of life and reproductive health. This narrative review aims to explore in detail the reproductive challenges associated with major hereditary NMDs, including Charcot-Marie-Tooth disease (CMT), dystrophinopathies, Myotonic Dystrophy (DM), Facioscapulohumeral Muscular Dystrophy (FSHD), Spinal Muscular Atrophy (SMA), Limb-Girdle Muscular Dystrophy (LGMD), and Amyotrophic Lateral Sclerosis (ALS). Specifically, it discusses the stages of diagnosis and genetic testing, recurrence risk estimation, options for preimplantation genetic testing (PGT) and prenatal diagnosis (PND), the reciprocal influence between pregnancy and disease, potential obstetric complications, and risks to the newborn.

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Article Synopsis
  • - Limb-girdle muscular dystrophy (LGMD) is a diverse group of genetic muscle diseases that can often be misdiagnosed due to their varied symptoms and progressions.
  • - A case study details a 56-year-old woman with late-onset LGMD R1/2A, who faced multiple health issues including elevated creatine kinase levels, limb fatigue, and heart problems that required a pacemaker.
  • - The study highlights the importance of early diagnosis and targeted treatments for LGMD, especially since this patient also had rare conditions like sick sinus syndrome and primary hyperparathyroidism, which complicate the clinical picture.
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The term limb-girdle muscular dystrophy (LGMD) refers to a variety of genetic neuromuscular disorders that typically affect the proximal muscles surrounding the hip and shoulder girdles. Despite having multiple genetic subtypes, these share similar clinical and imaging findings. Autosomal dominant forms are grouped under type 1, and autosomal recessive forms are grouped under type 2.

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Weekly Steroids in Muscular Dystrophy (WSiMD) was a pilot study to evaluate once weekly prednisone in patients with Limb Girdle and Becker muscular dystrophy (LGMD and BMD, respectively). At study endpoint, there were trends towards increased lean mass, reduced fat mass, reduced creatine kinase and improved motor function. The investigation was motivated by studies in mouse muscular dystrophy models in which once weekly glucocorticoid exposure enhanced muscle strength and reduced fibrosis.

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Background: Targeted next generation sequence analyses in a cohort of 961 previously described patients with clinically suspected Duchene muscular dystrophy (DMD) revealed that 145/961 (15%) had variants in genes associated with other muscular dystrophies (OMDs).

Methods: NGS was carried out in DMD negative patients after deletion/duplication analysis followed by WES for No variant cases.

Results: The majority of patients with OMDs had autosomal recessive diseases that included Limb-Girdle Muscular Dystrophies (LGMDs), Bethlem, Ullrich congenital Myopathies and Emery-Driefuss muscular dystrophy.

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TRIM32 inhibits Venezuelan equine encephalitis virus infection by targeting a late step in viral entry.

PLoS Pathog

November 2024

Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China.

Alphaviruses are mosquito borne RNA viruses that are a reemerging public health threat. Alphaviruses have a broad host range, and can cause diverse disease outcomes like arthritis, and encephalitis. The host ubiquitin proteasome system (UPS) plays critical roles in regulating cellular processes to control the infections with various viruses, including alphaviruses.

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Article Synopsis
  • Laminin α2-related muscular dystrophies are genetic disorders that can range from severe congenital forms to milder adult-onset versions, both transmitted in an autosomal recessive manner.
  • The report discusses two previously undiagnosed cases of this condition, where children exhibited sudden weakness and elevated creatine kinase levels, triggered by coxsackievirus infections.
  • Genetic testing revealed harmful variations in the LAMA2 gene for both children, confirming their diagnosis and showcasing that acute illness can lead to weakness in these cases.
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Cryo-EM structures of the membrane repair protein dysferlin.

Nat Commun

November 2024

Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, USA.

Plasma membrane repair in response to damage is essential for cell viability. The ferlin family protein dysferlin plays a key role in Ca-dependent membrane repair in striated muscles. Mutations in dysferlin lead to a spectrum of diseases known as dysferlinopathies.

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Article Synopsis
  • - Limb-girdle muscular dystrophies (LGMDs) are inherited disorders affecting skeletal muscles, and although there's no cure, rehabilitation can help in maintaining muscle strength and overall health.
  • - A systematic review of 560 articles identified 16 studies focusing on various rehabilitation strategies for LGMD, including neuromuscular training and respiratory interventions tailored to individual patient needs.
  • - Results show that personalized exercise programs can improve strength and psychological well-being, while generic protocols might lead to fatigue and pain; future research should explore the effects of rehabilitation on mental health and quality of life.
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Introduction And Aims: We describe a case of long-living COLQ-related congenital myasthenic syndrome (CMS) benefitting from ephedrine with an overall improvement quantified with functional measures.

Results: A 71-year-old man was referred with limb-girdle/axial myopathy and fatigability since infancy. In his thirties, a decremental response was observed at 3Hz-nerve stimulation, although testing seronegative for anti-neuromuscular junction antibodies.

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AAV-based TCAP delivery rescues mitochondria dislocation in limb-girdle muscular dystrophy R7.

Brain

October 2024

Department of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Diseases, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, China.

Article Synopsis
  • Limb-girdle muscular dystrophy R7 is a genetic disorder caused by mutations in the TCAP gene, leading to the absence of the protein telethonin and resulting in muscle weakness and mitochondrial dysfunction.
  • The research involves a Tcap-deficient mouse model to study the disease's mechanisms and potential treatments, using various experimental techniques like immunofluorescence and proteomics.
  • Findings reveal that telethonin is essential for maintaining desmin integrity and proper mitochondrial distribution, and experiments also explore gene therapy using adeno-associated virus to deliver the Tcap gene.
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Background: SELENON-related myopathy (SELENON-RM) is a rare congenital myopathy characterized by slowly progressive axial muscle weakness, rigidity of the spine, scoliosis, and respiratory insufficiency. Laminin-a2-related muscular dystrophy (LAMA2-MD) has a similar clinical phenotype, which ranges from severe, early-onset congenital muscular dystrophy type 1A (MDC1A) to milder forms presenting as childhood- or adult-onset limb-girdle type muscular dystrophy. The first 1.

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Lamin A/C is a protein encoded by the LMNA gene and belongs to the nuclear lamina protein family. Mutations in the LMNA gene lead to several diseases: Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease, and Hutchinson-Gilford progeria syndrome. In this study, a lamin A/C knockout human induced pluripotent stem cell line was successfully generated using the CRISPR/Cas9 genome-editing technology, which was confirmed with normal pluripotency and karyotype.

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Article Synopsis
  • Pathogenic variants in the FKRP gene cause various muscular dystrophies, including Limb-Girdle Muscular Dystrophy type 9 (LGMDR9), which is notably prevalent in Italy.
  • A study analyzed 153 patients from Southern Italy showing Duchenne/Becker-like symptoms, identifying pathogenic variants in 16 individuals, with specific variants frequently found.
  • The findings emphasize the need to include LGMDR9 in the diagnosis of dystrophinopathies, aiming to improve the identification and management of affected patients in Calabria.
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Article Synopsis
  • Muscular dystrophy (MD) is a genetic disorder characterized by muscle weakness, with a higher prevalence in regions like Iran due to common consanguineous marriages.
  • The study focused on three unrelated families with undiagnosed cases of MD and used whole exome sequencing (WES) to identify mutations in genes associated with collagen type VI.
  • The findings revealed specific mutations in the COL6A genes for each family, highlighting WES as a useful tool for diagnosing unidentified MD cases and expanding knowledge about its genetic causes in Iran.
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