842 results match your criteria: "Charcot-Marie-Tooth and Other Hereditary Motor and Sensory Neuropathies"

Connexins (Cxs) are fundamental in cell-cell communication, functioning as gap junction channels (GJCs) that facilitate solute exchange between adjacent cells and as hemichannels (HCs) that mediate solute exchange between the cytoplasm and the extracellular environment. Mutations in the GJB1 gene, which encodes Cx32, lead to X-linked Charcot-Marie-Tooth type 1 (CMTX1), a rare hereditary demyelinating disorder of the peripheral nervous system (PNS) without an effective cure or treatment. In Schwann cells, Cx32 HCs are thought to play a role in myelination by enhancing intracellular and intercellular Ca signaling, which is crucial for proper PNS myelination.

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Clinical Outcome Assessments and Biomarkers in Charcot-Marie-Tooth Disease.

Neurology

December 2024

From the Department of Neurology (B.A.M.), University of Michigan Medical School, Ann Arbor; and Department of Neurology (V.F.), University of Colorado Anschutz Medical Campus, Aurora.

Charcot-Marie-Tooth disease (CMT) encompasses a diverse group of genetic forms of inherited peripheral neuropathy and stands as the most common hereditary neurologic disease worldwide. At present, no disease-modifying treatments exist for any form of CMT. However, promising therapeutic strategies are rapidly emerging, necessitating careful consideration of clinical outcome assessments (COAs) and clinical trial design.

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Synergistic effect of Wharton's jelly-derived mesenchymal stem cells and insulin on Schwann cell proliferation in Charcot-Marie-Tooth disease type 1A treatment.

Neurobiol Dis

December 2024

Cell & Gene Therapy Research Institute, ENCell Co. Ltd., Seoul 06072, Republic of Korea; Cell and Gene Therapy Institute, Samsung Medical Center, Seoul 06351, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea. Electronic address:

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Myotubularin-Related Protein 5 (MTMR5) is an inactive, poorly characterized D3-phosphatidylinositol phosphatase. Mutations in MTMR5 have been linked to Charcot-Marie-Tooth Disease Type 4B3 (CMT4B3), a rare, early-onset, recessive peripheral neuropathy. Here, we describe the establishment and validation of three human induced pluripotent stem cell (iPSC) lines derived from unrelated CMT4B3 patients, each harboring homozygous MTMR5/Sbf1 mutations.

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: The genetic underpinnings of Parkinson's disease (PD) and parkinsonism have drawn increasing attention in recent years. Mutations in the Factor-Induced Gene 4 ( have been implicated in various neurological disorders, including Charcot-Marie-Tooth disease type 4J (CMT4J), amyotrophic lateral sclerosis (ALS), and Yunis-Varón syndrome. This review aims to explore the association between mutations and parkinsonism, with a specific focus on the rare missense mutation p.

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Charcot-Marie-Tooth disease type 2N (CMT2N) is an inherited nerve disorder caused by mutations in the alanyl-tRNA synthetase (AlaRS) gene, resulting in muscle weakness and sensory issues. Currently, there is no cure for CMT2N. Here, we found that all five AlaRS mutations in the aminoacylation domain can interact with neuropilin-1 (Nrp1), which is consistent with our previous findings.

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Pharmacologically increasing cGMP improves proteostasis and reduces neuropathy in mouse models of CMT1.

Cell Mol Life Sci

October 2024

Department of Biochemistry, Institute for Myelin and Glia Exploration, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, 14203, USA.

Increasing cyclic GMP activates 26S proteasomes via phosphorylation by Protein Kinase G and stimulates the intracellular degradation of misfolded proteins. Therefore, agents that raise cGMP may be useful therapeutics against neurodegenerative diseases and other diseases in which protein degradation is reduced and misfolded proteins accumulate, including Charcot Marie Tooth 1A and 1B peripheral neuropathies, for which there are no treatments. Here we increased cGMP in the S63del mouse model of CMT1B by treating for three weeks with either the phosphodiesterase 5 inhibitor tadalafil, or the brain-penetrant soluble guanylyl cyclase stimulator CYR119.

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Effect of Pathogenic Mutations on the Formation of High-Order Dynamin 2 Assemblies in Living Cells.

Biochemistry

November 2024

Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii 96813, United States.

Article Synopsis
  • Mutations in dynamin 2 (DNM2) are linked to two movement disorders: Charcot-Marie-Tooth neuropathies (CMT) and centronuclear myopathy (CNM), primarily affecting the pleckstrin homology domain (PHD).
  • CNM mutations disrupt intramolecular interactions that normally inhibit DNM2 activity, while CMT mutations are mostly on a different part of the PHD that is involved in binding phosphoinositides, leading to distinct disease outcomes.
  • Research reveals that both DNM2 and CNM-linked mutants create larger, more stable structures in the plasma membrane compared to wild-type DNM2, but CNM mutations appear to have a stronger impact, causing more
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Background And Aims: The Charcot-Marie-Tooth Disease Health Index (CMT-HI) is a disease-specific, patient-reported disease burden measure. As part of an international clinical trial readiness study, individuals with CMT1A (ages 18-75 years) underwent clinical outcome assessments (COAs), including the CMT-HI, to capture their longitudinal perspective on the disease burden.

Methods: Two hundred and fifteen participants underwent serial COAs including the CMT-HI, CMT Functional Outcome Measure (CMT-FOM), CMT Neuropathy Score (CMTNSv2R), and CMT Exam Score (CMTES/CMTES-R).

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Sensory-Motor Neuropathy in Mfn2 T105M Knock-in Mice and Its Reversal by a Novel Piperine-Derived Mitofusin Activator.

J Pharmacol Exp Ther

October 2024

Department of Internal Medicine (Pharmacogenomics), Washington University School of Medicine (J.W., L.Z., A.F., E.C., G.W.D.) and Mitochondria in Motion, Inc. (J.W., L.Z.), St. Louis Missouri

Mitochondrial dysfunction is a hallmark of many genetic neurodegenerative diseases, but therapeutic options to reverse mitochondrial dysfunction are limited. While recent studies support the possibility of improving mitochondrial fusion/fission dynamics and motility to correct mitochondrial dysfunction and resulting neurodegeneration in Charcot-Marie-Tooth disease (CMT) and other neuropathies, the clinical utility of reported compounds and relevance of preclinical models are uncertain. Here, we describe motor and sensory neuron dysfunction characteristic of clinical CMT type 2 A in a CRISPR/Casp-engineered Mfn2 Thr105Met (T105M) mutant knock-in mouse.

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Introduction: Ankle-foot orthoses (AFOs) are commonly prescribed for people with Charcot-Marie-Tooth disease (CMT) to improve gait efficiency and reduce the occurrence of tripping and falls. The aim of this study was to systematically review evidence on the effects of AFOs on gait kinematics and kinetics and postural stability/balance in people with CMT.

Methods: Studies were identified from electronic databases and screened for inclusion online using Rayyan.

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Article Synopsis
  • * Methods involved measuring peak exercise-induced blood flow, echointensity, and echotexture in elbow flexor muscles of patients with various dystrophies and comparing them to healthy controls.
  • * Results showed that muscle blood flow was significantly lower in all patient groups compared to controls, especially in BMD patients, indicating that reduced blood flow correlates with altered echotexture and muscle strength; this suggests muscle
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We aimed to develop efficient data labeling strategies for ground truth segmentation in lower-leg magnetic resonance imaging (MRI) of patients with Charcot-Marie-Tooth disease (CMT) and to develop an automated muscle segmentation model using different labeling approaches. The impact of using unlabeled data on model performance was further examined. Using axial T1-weighted MRIs of 120 patients with CMT (60 each with mild and severe intramuscular fat infiltration), we compared the performance of segmentation models obtained using several different labeling strategies.

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Background And Aims: Ultrasound nerve cross-sectional area (CSA) of patients affected with axonal neuropathy usually shows normal value. Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) seems to represent an exception, showing smaller CSA, but previous reports did not test for biallelic RFC1 gene repeat expansions.

Methods: We compared nerve CSA from CANVAS patients (tested positive for biallelic RFC1 gene repeat expansions) with the CSA from a group of patients with chronic idiopathic axonal polyneuropathy (CIAP) who tested negative for RFC1 gene repeat expansions, hereditary axonal neuropathy (Charcot-Marie-Tooth type 2, CMT2), and Friedreich ataxia (FRDA).

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Hidden hearing loss (HHL), a recently described auditory neuropathy characterized by normal audiometric thresholds but reduced sound-evoked cochlear compound action potentials, has been proposed to contribute to hearing difficulty in noisy environments in people with normal hearing thresholds and has become a widespread complaint. While most studies on HHL pathogenesis have focused on inner hair cell (IHC) synaptopathy, we recently showed that transient auditory nerve (AN) demyelination also causes HHL in mice. To test the effect of myelinopathy on hearing in a clinically relevant model, we studied a mouse model of Charcot-Marie-Tooth type 1A (CMT1A), the most prevalent hereditary peripheral neuropathy in humans.

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Charcot-Marie-Tooth disease type 1E (CMT1E) is an inherited autosomal dominant peripheral neuropathy caused by mutations in the peripheral myelin protein 22 (PMP22) gene. The identical leucine-to-proline (L16P) amino acid substitution in PMP22 is carried by the Trembler J (TrJ) mouse and is found in CMT1E patients presenting with early-onset disease. Peripheral nerves of patients diagnosed with CMT1E display a complex and varied histopathology, including Schwann cell hyperproliferation, abnormally thin myelin, axonal degeneration, and subaxonal morphological changes.

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Validity of Cardiopulmonary Exercise Testing for Assessing Aerobic Capacity in Neuromuscular Diseases.

Arch Phys Med Rehabil

October 2024

Department of Rehabilitation Medicine, Amsterdam UMC location, University of Amsterdam, Amsterdam; Amsterdam Movement Sciences, Rehabilitation & Development, Amsterdam, The Netherlands. Electronic address:

Objectives: To determine the content validity of cardiopulmonary exercise testing (CPET) for assessing peak oxygen uptake (VO) in neuromuscular diseases (NMD).

Design: Baseline assessment of a randomized controlled trial.

Setting: Academic hospital.

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Pathogenic, biallelic variants in were identified in 2020 as a novel cause for autosomal-recessive Charcot-Marie-Tooth disease (CMT) type 2, an inherited neuropathy. codes for the enzyme sorbitol dehydrogenase. Loss of this enzyme's activity leads to an increase of sorbitol in serum.

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Dominant missense mutations of the calcium-permeable cation channel TRPV4 cause Charcot-Marie-Tooth disease (CMT) type 2C and two forms of distal spinal muscular atrophy. These conditions are collectively referred to as TRPV4-related neuromuscular disease and share features of motor greater than sensory dysfunction and frequent vocal fold weakness. Pathogenic variants lead to gain of ion channel function that can be rescued by TRPV4 antagonists in cellular and animal models.

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Background: We aimed to investigate the clinical features of a large cohort of patients with myelin protein zero ()-related neuropathy, focusing on the five main mutation clusters across Italy.

Methods: We retrospectively gathered a minimal data set of clinical information in a series of patients with these frequent mutations recruited among Italian Charcot-Marie-Tooth (CMT) registry centres, including disease onset/severity (CMTES-CMT Examination Score), motor/sensory symptoms and use of orthotics/aids.

Results: We collected data from 186 patients: 60 had the p.

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Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited peripheral neuropathy caused by a 1.5 Mb tandem duplication of chromosome 17 harbouring the PMP22 gene. This dose-dependent overexpression of PMP22 results in disrupted Schwann cell myelination of peripheral nerves.

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Distal hereditary motor neuropathies.

Rev Neurol (Paris)

December 2024

Neurosciences Laboratory, University Benyoucef Benkhedda, Algiers, Algeria; Department of Neurology, EHS El Maham, Cherchell,Tipaza, Algeria.

Distal hereditary motor neuropathies (dHMN) are a group of heterogeneous hereditary disorders characterized by a slowly progressive distal pure motor neuropathy. Electrophysiology, with normal motor and sensory conduction velocities, can suggest the diagnosis of dHMN and guide the genetic study. More than thirty genes are currently associated with HMNs, but around 60 to 70% of cases of dHMN remain uncharacterized genetically.

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Demyelinating Charcot-Marie-Tooth 4G (CMT4G) results from a recessive mutation in the 5'UTR region of the Hexokinase 1 (HK1) gene. HK participates in mitochondrial calcium homeostasis by binding to the Voltage-Dependent Anion Channel (VDAC), through its N-terminal porin-binding domain. Our hypothesis is that CMT4G mutation results in a broken interaction between mutant HK1 and VDAC, disturbing mitochondrial calcium homeostasis.

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Purpose: This study describes how the diagnosis of Usher syndrome was revised to PRPS1-associated retinopathy and Charcot-Marie-Tooth disease type 5.

Case Report: A 38-year-old female with bilaterally subnormal vision and non-congenital hearing loss was initially diagnosed with Usher syndrome, based on finding variants in three genes (MYO7A, USH2A, and PCDH15), was re-evaluated at the inherited retinal disorders clinic. She had asymmetric retinopathy and right macular pseudocoloboma.

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