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Research

A translatable RNAi-driven gene therapy silences PMP22/Pmp22 genes and improves neuropathy in CMT1A mice May 17, 2022 - AAV9-miR871-driven silencing of PMP22 rescues a CMT1A model and provides proof of principle for treating CMT1A using a translatable gene therapy approach.
Molecular characterization of Turkish patients with demyelinating Charcot-Marie-Tooth disease May 13, 2022 - Many therapeutic strategy options including promising small-molecular compounds, gene replacement therapy, or disease-modifying therapies will soon be implemented in the clinical setting.
Do different foot types affect the 6-min walk test capacity of younths with Charcot-Marie-Tooth neuropathy ? May 12, 2022 - Performance was decreased in youths with CMT in comparison to non-CMT. Contrary to what was expected, the cavus foot type did not show lower gait capacity than the flatfoot, suggesting that the types of feet alone did not determine differences in gait capacity within the CMT group.
Effective treatment of advanced Hodgkin lymphoma with a modified BEACOPP regimen for a patient with demyelinating hereditary motor and sensory neuropathy type 1 (HMSN1) May 5, 2022 - The patient with Charcot-Marie-Tooth disease or HSMN1 and advanced Hodgkin lymphoma undergoing treatment with modified BEACOPP achieving complete remission without major aggravation of neurological symptoms.
Structural insights into Charcot-Marie-Tooth disease-linked mutations in human GDAP1 May 4, 2022 - CMT may arise from disruption of specific intra- and intermolecular interaction networks, leading to alterations in GDAP1 structure and stability, and eventually, insufficient motor and sensory neuron function.
Treatment with IFB-088 Improves Neuropathy in CMT1A and CMT1B Mice May 2, 2022 - IFB-088 reduces the amount of newly synthesized proteins entering the ER, allowing the protein quality control systems to better cope with the unfolded/misfolded protein and allowing myelination to progress.
Novel de novo POLR3B mutations responsible for demyelinating Charcot-Marie-Tooth disease in Japan Apr 28, 2022 - POLR3B mutations should be added to the CMT-related gene panel for comprehensive genetic screening.
Generation of a human induced pluripotent stem cell (iPSC) line (JUCTCi019-A) from a patient with Charcot-Marie-Tooth disease type 2A2 (CMT2A2) due to a heterozygous missense substitution c.2119C > T (p.Arg707Trp) in MFN2 gene Apr 12, 2022 - This iPSC line represents an ideal source for disease modelling and drug development of CMT2A2 disease.
Dosage effects of PMP22 on nonmyelinating Schwann cells in hereditary neuropathy with liability to pressure palsies Apr 8, 2022 - PMP22 dosage affects nonmyelinating as well as myelinating Schwann cells.
The Antiepileptic Valproic Acid Ameliorates Charcot-Marie-Tooth 2W (CMT2W) Disease-Associated HARS1 Mutation-Induced Inhibition of Neuronal Cell Morphological Differentiation Through c-Jun N-terminal Kinase Apr 5, 2022 - This could be a potential therapeutic drug for CMT2W at the cellular levels.
Therapeutic Potential of CKD-504, a Novel Selective Histone Deacetylase 6 Inhibitor Mar 30, 2022 - Therefore, our results suggest that the novel HDAC6 inhibitor CKD-504 could be a potential therapeutic approach for NMJ diseases such as CMT and dHMN5.
Curcumin and Ethanol Effects in Trembler-J Schwann Cell Culture Mar 29, 2022 - The analysis of the effects of the vehicle itself is an essential and inescapable step to comprehensibly assess the effects and full potential of curcumin treatment for therapeutic purposes.
The Role of Impaired Mitochondrial Dynamics in MFN2-Mediated Pathology Mar 24, 2022 - Here, we will review what is known about the various functions of MFN2 that are impaired by pathogenic variants causing CMT2A, with a specific emphasis on the ties between MFN2 variants and MERCs.
HDAC3 Inhibition Stimulates Myelination in a CMT1A Mouse Model Mar 23, 2022 - Overall, our results indicate that correct dosing of HDAC3 inhibitors is of crucial importance if translated to a clinical setting for demyelinating forms of CMT or other neurological disorders.
Mitochondrial Phenotypes in Genetically Diverse Neurodegenerative Diseases and Their Response to Mitofusin Activation Mar 21, 2022 - Pharmacological MFN activation of metabolically reprogrammed fibroblasts partially reversed the mitochondrial abnormalities in CMT2A and CMT1 and a subset of Parkinson’s and Alzheimer’s disease patients, implicating addressable mitochondrial dysdynamism in these illnesses.
Clinical genetics of Charcot–Marie–Tooth disease Mar 18, 2022 - In addition, we discuss the newly identified novel causative genes for CMT/IPNs in Japan, namely MME and COA7. Identification of the new causes of CMT will facilitate in-depth characterization of the underlying molecular mechanisms of CMT, leading to the establishment of therapeutic approaches such as drug development and gene therapy.
Unexpected Intermediate Nerve Conduction Velocity Findings in Charcot-Marie-Tooth Syndromes Classified as Demyelinated or Axonal in a Pediatric Population Mar 16, 2022 - Unexpected Intermediate Nerve Conduction Velocity Findings in Charcot-Marie-Tooth Syndromes Classified as Demyelinated or Axonal in a Pediatric Population https://pubmed.ncbi.nlm.nih.gov/35297028/ https://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-0042-1743438
DNAJB2-related Charcot-Marie-Tooth disease type 2: Pathomechanism insights and phenotypic spectrum widening Mar 14, 2022 - Our results broaden the clinical spectrum of DNAJB2-related neuropathies and provide evidence that DNAJB2 mutations should be taken into account as another causative gene of CMT2 with hearing loss and parkinsonism.
Multiubiquitination of TRPV4 reduces channel activity independent of surface localization Mar 14, 2022 - Together, these data reveal a novel mechanism via which ubiquitination of an intracellular flexible IDR domain modulates ion channel function independently of endocytic trafficking and identify a contributory role for this pathway in the dysregulation of TRPV4 channel activity by neuropathy-causing mutations. (Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C.)
Mitochondria-lysosome contact site dynamics and misregulation in neurodegenerative diseases Mar 3, 2022 - Defects in mitochondria-lysosome contacts have been observed in experimental models of genetic mutations associated with multiple neurodegenerative diseases, including Charcot-Marie-Tooth disease. In this review, we highlight recent advances in the field of mitochondria-lysosome contact sites and their misregulation across multiple neurodegenerative disorders, which further underscore a potential role for this pathway in neuronal homeostasis and disease.
Acute to Subacute Atraumatic Entrapment Neuropathies in Patients With CMT1A: A Report of a Distinct Phenotypic Variant of CMT1A Feb 25, 2022 - We propose that CMT1A with acute to subacute, atraumatic, entrapment neuropathies to be a distinct phenotypic variant of CMT1A.
Early targeting of endoneurial macrophages alleviates the neuropathy and affects abnormal Schwann cell differentiation in a mouse model of Charcot-Marie-Tooth 1A Feb 21, 2022 - These findings underscore the targetable role of macrophage-mediated inflammation in peripheral nerves of inherited neuropathies, but also emphasize the need for an early treatment start confined to a narrow therapeutic time window in CMT1A models and potentially in respective patients.
Structural insights into Charcot-Marie-Tooth disease-linked mutations in human GDAP1 [preprint] Feb 18, 2022 - Taken together, although the CMT mutations in GDAP1 initially appear to be scattered throughout the sequence, in the 3D structure, they are involved in close interaction networks, and these networks are sensitive against changes in many different participating residues. This observation explains the general loss of protein stability upon mutations in such networks and clusters and may hint at an overall mechanism of GDAP1-linked CMT.
Neurofilament Light Regulates Axon Caliber, Synaptic Activity, and Organelle Trafficking in Cultured Human Motor Neurons Feb 14, 2022 - Dominant missense mutations and recessive nonsense mutations in the neurofilament light gene (NEFL) are among the causes of Charcot–Marie–Tooth (CMT) neuropathy, which affects the peripheral nerves with the longest axons.
A splice altering variant in NDRG1 gene causes Charcot-Marie-Tooth disease, type 4D Feb 11, 2022 - https://link.springer.com/article/10.1007/s10072-022-05893-4 A splice altering variant in NDRG1 gene causes Charcot-Marie-Tooth disease, type 4D
NCAM1 and GDF15 are biomarkers of Charcot-Marie-Tooth disease in patients and mice Feb 10, 2022 - We also identify serum GDF15 as a highly sensitive diagnostic biomarker, which was elevated in all CMT genotypes as well as in Hspb8K141N, Gjb1-null, GarsC201R and GarsP278KY mouse models.
Neuropathic pain in Charcot-Marie-Tooth Disease Feb 7, 2022 - NP prevalence varies among CMTs subtypes and is mainly related to Aδ fibers impairment. #NP
Heterozygous POLG variant Ser1181Asn co-segregating in a family with autosomal dominant axonal neuropathy, proximal muscle fatigability, ptosis, and ragged red fibers Feb 1, 2022 - https://pubmed.ncbi.nlm.nih.gov/35101151/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220201133212&v=2.17.5 Heterozygous POLG variant Ser1181Asn co-segregating in a family with autosomal dominant axonal neuropathy, proximal muscle fatigability, ptosis, and ragged red fibers By whole-exome sequencing, we found the heterozygous POLG variant c.3542G>A; p.Ser1181Asn in a family of four affected individuals, presenting with a mixed neuro-myopathic phenotype. The variant is located within the active site of polymerase gamma, in a cluster region associated with an autosomal dominant inheritance. In adolescence, the index developed distal atrophies and weakness, sensory loss, afferent ataxia, double vision, and bilateral ptosis. One older sister presented with... pubmed:35101151
Autophagy and Lysosomal Functionality in CMT2B Fibroblasts Carrying the RAB7K126R Mutation Jan 31, 2022 - https://www.mdpi.com/2073-4409/11/3/496
Cavovarus with A Twist: Coronal and Axial Plane Rotational Deformity in the Midfoot of Charcot- Marie-Tooth Patients Jan 31, 2022 - https://pubmed.ncbi.nlm.nih.gov/35097497/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220131075933&v=2.17.5 Cavovarus with A Twist: Coronal and Axial Plane Rotational Deformity in the Midfoot of Charcot- Marie-Tooth Patients No abstract pubmed:35097497
Use of Weight-Bearing Computed Tomography in the Evaluation of Abnormal Hindfoot Morphology in Charcot-Marie-Tooth Patients Jan 31, 2022 - https://pubmed.ncbi.nlm.nih.gov/35097541/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220131075933&v=2.17.5 Use of Weight-Bearing Computed Tomography in the Evaluation of Abnormal Hindfoot Morphology in Charcot-Marie-Tooth Patients No abstract pubmed:35097541
Popliteal Nerve Catheters for Perioperative Pain Control in Charcot-Marie-Tooth Patients Jan 31, 2022 - https://pubmed.ncbi.nlm.nih.gov/35097573/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220131075933&v=2.17.5 Popliteal Nerve Catheters for Perioperative Pain Control in Charcot-Marie-Tooth Patients No abstract pubmed:35097573
Clinically Significant Improvement in Pre vs Post-Operative PROMIS Scores after Cavovarus Reconstruction in Patients with Charcot-Marie-Tooth Disease Jan 31, 2022 - https://pubmed.ncbi.nlm.nih.gov/35097718/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220131075933&v=2.17.5 Clinically Significant Improvement in Pre vs Post-Operative PROMIS Scores after Cavovarus Reconstruction in Patients with Charcot-Marie-Tooth Disease No abstract pubmed:35097718
Development of a standard of care for patients with valosin-containing protein associated multisystem proteinopathy Jan 31, 2022 - https://pubmed.ncbi.nlm.nih.gov/35093159/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220131015242&v=2.17.5 Development of a standard of care for patients with valosin-containing protein associated multisystem proteinopathy Valosin-containing protein (VCP) associated multisystem proteinopathy (MSP) is a rare inherited disorder that may result in multisystem involvement of varying phenotypes including inclusion body myopathy, Paget's disease of bone (PDB), frontotemporal dementia (FTD), parkinsonism, and amyotrophic lateral sclerosis (ALS), among others. An international multidisciplinary consortium of 40+ experts in neuromuscular disease, dementia, movement disorders, psychology, cardiology, pulmonology, physical... pubmed:35093159
The protective role of mesencephalic astrocyte-derived neurotrophic factor in endoplasmic reticulum stress in RT4-D6P2T schwannoma sells with the S63del MPZ mutation Jan 29, 2022 - https://pubmed.ncbi.nlm.nih.gov/35090307/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220129090937&v=2.17.5 The protective role of mesencephalic astrocyte-derived neurotrophic factor in endoplasmic reticulum stress in RT4-D6P2T schwannoma sells with the S63del MPZ mutation CONCLUSIONS: ERS occurred in RT4-D6P2T cells with S63del MPZ mutation, and MANF exerted protective effect in RT4-D6P2T cells with S63del MPZ mutation. pubmed:35090307
An NEFH founder mutation causes broad phenotypic spectrum in multiple Japanese families Jan 29, 2022 - https://pubmed.ncbi.nlm.nih.gov/35091664/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220129090937&v=2.17.5 An NEFH founder mutation causes broad phenotypic spectrum in multiple Japanese families BACKGROUND AND AIMS: Mutations in neurofilament genes have been linked to several neuromuscular disorders. The neurofilament heavy (NEFH) gene was identified as the causative gene of Charcot-Marie-Tooth disease type 2CC (CMT2CC) in 2016, with a toxic gain of function mechanism caused by the translation and aggregation of cryptic amyloidogenic element (CAE) in the 3' untranslated region (UTR). But the NEFH-related clinical and genetic spectrums are still unclear in Japan. pubmed:35091664
Cytokines secreted by mesenchymal stem cells reduce demyelination in an animal model of Charcot-Marie-Tooth disease Jan 28, 2022 - Further elucidation of the underlying mechanisms of GDF-15 and AREG in myelination might provide a robust basis for the development of effective therapies against demyelinating CMT.
SARM1 Knockout Does Not Rescue Neuromuscular Phenotypes in a Charcot-Marie-Tooth Disease Type 1A Mouse Model Jan 28, 2022 - The study found that the mice served in CMT1A mice are likely caused primarily by prolonged dysmyelination.
Whole-exome sequencing identifies a novel de novo variant in DYNC1H in a patient with intractable epilepsy Jan 28, 2022 - https://pubmed.ncbi.nlm.nih.gov/35088241/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220128074134&v=2.17.5 Whole-exome sequencing identifies a novel de novo variant in DYNC1H in a patient with intractable epilepsy DYNC1H1 variants are associated with broad phenotypes including Charcot-Marie-Tooth disease, spinal muscular atrophy, and mental retardation. However, DYNC1H1 variants related intractable epilepsy have not yet been described in detail so far. Herein, we describe the detailed clinical manifestations of a female patient, carrying a novel de novo variant in DYNC1H1 (p.H311Y), who presented with malformation of cortical development (MCD), refractory epilepsy, intellectual disability, and lower motor... pubmed:35088241
Proximal nerve MR neurography with diffusion tensor imaging in differentiating subtypes of Charcot-Marie-Tooth disease Jan 27, 2022 - https://pubmed.ncbi.nlm.nih.gov/35084519/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220127142411&v=2.17.5 Proximal nerve MR neurography with diffusion tensor imaging in differentiating subtypes of Charcot-Marie-Tooth disease CONCLUSIONS: MR neurography with DTI is able to differentiate CMT1A patients, CMT2 patients, and healthy controls. pubmed:35084519
Validation of the Spanish version of the Charcot-Marie-Tooth disease Pediatric Scale (CMTPedS) Jan 27, 2022 - https://pubmed.ncbi.nlm.nih.gov/35084732/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220127142411&v=2.17.5 Validation of the Spanish version of the Charcot-Marie-Tooth disease Pediatric Scale (CMTPedS) CONCLUSIONS: The Spanish version of the CMTPedS can be used for monitoring and conducting clinical trials in the Spanish population and in Spanish-speaking countries. pubmed:35084732
Foot orthoses for treating paediatric flat feet Jan 26, 2022 - https://pubmed.ncbi.nlm.nih.gov/35080267/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220126150809&v=2.17.5 Foot orthoses for treating paediatric flat feet BACKGROUND: Paediatric flat feet are a common presentation in primary care; reported prevalence approximates 15%. A minority of flat feet can hurt and limit gait. There is no optimal strategy, nor consensus, for using foot orthoses (FOs) to treat paediatric flat feet. pubmed:35080267
Diagnosis of a floppy neonate with misleading clues: unraveled as congenital hypomyelinating neuropathy Jan 25, 2022 - https://pubmed.ncbi.nlm.nih.gov/35058287/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220125013506&v=2.17.5 Diagnosis of a floppy neonate with misleading clues: unraveled as congenital hypomyelinating neuropathy Contactin-associated protein 1 (CNTNAP1)-related congenital hypomyelinating neuropathy (CHN) is a rare type of peripheral neuropathy and has a clinically heterogeneous presentation. We report a neonate with an atypical presentation in the form of global hypotonia, facial diparesis and partial response to neostigmine challenge test. There was no clinical improvement on initiation of anticholinesterase drug for suspected congenital myasthenia and hence stopped. Detection of a pathogenic variant in... pubmed:35058287
Imbalance of Neuregulin1-ErbB2/3 signaling underlies altered myelin homeostasis in models of Charcot-Marie-Tooth disease type 4H [preprint] Jan 22, 2022 - Overall, our work reveals a new role of FRABIN in the regulation of NRG1 type III/ErbB2/3 NRG1signaling and myelination and opens future therapeutic strategies based on the modulation of NRG1 type III/ErbB2/3 NRG1to reduce CMT4H pathology and more generally others demyelinating CMT.
Heterozygous DHTKD1 Variants in Two European Cohorts of Amyotrophic Lateral Sclerosis Patients Jan 21, 2022 - https://pubmed.ncbi.nlm.nih.gov/35052424/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220121121207&v=2.17.5 Heterozygous DHTKD1 Variants in Two European Cohorts of Amyotrophic Lateral Sclerosis Patients Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive upper and lower motor neuron (LMN) loss. As ALS and other neurodegenerative diseases share genetic risk factors, we performed whole-exome sequencing in ALS patients focusing our analysis on genes implicated in neurodegeneration. Thus, variants in the DHTKD1 gene encoding dehydrogenase E1 and transketolase domain containing 1 previously linked to 2-aminoadipic and 2-oxoadipic aciduria,... pubmed:35052424
Therapeutic Strategies Targeting Mitochondrial Calcium Signaling: A New Hope for Neurological Diseases? Jan 21, 2022 - https://pubmed.ncbi.nlm.nih.gov/35052668/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220121121207&v=2.17.5 Therapeutic Strategies Targeting Mitochondrial Calcium Signaling: A New Hope for Neurological Diseases? Calcium (Ca^(2+)) is a versatile secondary messenger involved in the regulation of a plethora of different signaling pathways for cell maintenance. Specifically, intracellular Ca^(2+) homeostasis is mainly regulated by the endoplasmic reticulum and the mitochondria, whose Ca^(2+) exchange is mediated by appositions, termed endoplasmic reticulum-mitochondria-associated membranes (MAMs), formed by proteins resident in both compartments. These tethers are essential to manage the mitochondrial... pubmed:35052668
An Integrated Approach to Studying Rare Neuromuscular Diseases Using Animal and Human Cell-Based Models Jan 20, 2022 - https://pubmed.ncbi.nlm.nih.gov/35047510/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220120134539&v=2.17.5 An Integrated Approach to Studying Rare Neuromuscular Diseases Using Animal and Human Cell-Based Models As sequencing technology improves, the identification of new disease-associated genes and new alleles of known genes is rapidly increasing our understanding of the genetic underpinnings of rare diseases, including neuromuscular diseases. However, precisely because these disorders are rare and often heterogeneous, they are difficult to study in patient populations. In parallel, our ability to engineer the genomes of model organisms, such as mice or rats, has gotten increasingly efficient through... pubmed:35047510
Phenotypic heterogeneity in patients with NEFL-related Charcot-Marie-Tooth disease Jan 19, 2022 - https://pubmed.ncbi.nlm.nih.gov/35044100/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220119131957&v=2.17.5 Phenotypic heterogeneity in patients with NEFL-related Charcot-Marie-Tooth disease Charcot-Marie-Tooth disease (CMT) is the most common hereditary peripheral neuropathy. Mutations in the neurofilament light polypeptide (NEFL) gene produce diverse clinical phenotypes, including demyelinating (CMT1F), axonal (CMT2E), and intermediate (CMTDIG) neuropathies. From 2005 to 2020, 1,143 Korean CMT families underwent gene sequencing, and we investigated the clinical, genetic, and neuroimaging spectra of NEFL-related CMT patients. Ten NEFL mutations in 17 families (1.49%) were... pubmed:35044100
Cavovarus With a Twist: Midfoot Coronal and Axial Plane Rotational Deformity in Charcot-Marie-Tooth Disease Jan 17, 2022 - https://pubmed.ncbi.nlm.nih.gov/35037521/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220117183032&v=2.17.5 Cavovarus With a Twist: Midfoot Coronal and Axial Plane Rotational Deformity in Charcot-Marie-Tooth Disease CONCLUSION: This 3-dimensional WBCT analysis is the first to isolate and quantify the multiplanar rotational deformity in the midfoot of CMT patients. Compared with healthy unmatched control cases, CMT patients demonstrated increased axial plane adduction and coronal plane rotation at the talonavicular (TN) joint. These findings support performing soft tissue release at the TN joint to abduct and derotate the midfoot as a first step for targeted deformity correction. pubmed:35037521
Therapeutic Strategies Targeting Mitochondrial Calcium Signaling: A New Hope for Neurological Diseases? Jan 15, 2022 - https://www.mdpi.com/2076-3921/11/1/165/htm https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8773297/ Therapeutic Strategies Targeting Mitochondrial Calcium Signaling: A New Hope for Neurological Diseases?
Foot orthoses for treating paediatric flat feet Jan 14, 2022 - https://pubmed.ncbi.nlm.nih.gov/35029841/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220114191813&v=2.17.5 Foot orthoses for treating paediatric flat feet BACKGROUND: Paediatric flat feet are a common presentation in primary care; reported prevalence approximates 15%. A minority of flat feet can hurt and limit gait. There is no optimal strategy, nor consensus, for using foot orthoses (FOs) to treat paediatric flat feet. pubmed:35029841
Elderly patients with suspected Charcot-Marie-Tooth disease should be tested for the TTR gene for effective treatments Jan 14, 2022 - https://pubmed.ncbi.nlm.nih.gov/35027655/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220114070517&v=2.17.5 Elderly patients with suspected Charcot-Marie-Tooth disease should be tested for the TTR gene for effective treatments BACKGROUND AND AIMS: Some hereditary transthyretin (ATTRv) amyloidosis patients are misdiagnosed as Charcot-Marie-Tooth disease (CMT) at onset. We assess the findings to identify ATTRv amyloidosis among patients with suspected CMT to screen transthyretin gene variants for treatments. pubmed:35027655
Tongue atrophy as a neurological finding in hereditary polyneuropathy in Alaskan malamutes Jan 12, 2022 - https://pubmed.ncbi.nlm.nih.gov/35019187/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220112131950&v=2.17.5 Tongue atrophy as a neurological finding in hereditary polyneuropathy in Alaskan malamutes CONCLUSION AND CLINICAL IMPORTANCE: Histopathologic changes in the tongue and hypoglossal nerve were consistent with previously reported changes in skeletal muscle and other nerves from dogs with AMPN. Therefore, we conclude that macroscopic tongue atrophy is part of the disease phenotype of AMPN and should be considered a potential clinical sign in dogs with polyneuropathies. pubmed:35019187
Neuropathic Ulcer Jan 11, 2022 - https://pubmed.ncbi.nlm.nih.gov/32644640/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220111054602&v=2.17.5 Neuropathic Ulcer Neuropathy is a broad term that describes a lack of sensorium, movement, or autonomic function and feedback in a particular area. This can be a centralized neuropathy due to paralysis of extremities via distribution of neurotomes, or a peripheralized neuropathy. Most commonly seen in the extremities is a varying degree of peripheral neuropathy. Peripheral neuropathy usually affects only the extremities and can have multiple sources of causality, with the most likely being diabetic peripheral... pubmed:32644640
Coexistence of Charcot-Marie-Tooth 1A and nondystrophic myotonia due to PMP22 duplication and SCN4A pathogenic variants: a case report Jan 8, 2022 - https://pubmed.ncbi.nlm.nih.gov/34996390/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220108094207&v=2.17.5 Coexistence of Charcot-Marie-Tooth 1A and nondystrophic myotonia due to PMP22 duplication and SCN4A pathogenic variants: a case report CONCLUSION: This study reports the coexistence of PMP22 duplication and SCN4A mutation. The presenting features in this family suggested that both neuropathy and myopathy were inherited in an autosomal dominant manner. The proband had a typical phenotype of sodium channel myotonia (SCM) and CMT1A. However, his father with the same mutations presented a much milder clinical phenotype. Our study might expand the genetic and phenotypic spectra of neuromuscular disorders with concomitant mutations. pubmed:34996390
Pathological evidence of demyelination in the recurrent laryngeal, phrenic, and oculomotor nerves in Charcot-Marie-Tooth disease 4F Jan 7, 2022 - https://pubmed.ncbi.nlm.nih.gov/34993357/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220107142648&v=2.17.5 Pathological evidence of demyelination in the recurrent laryngeal, phrenic, and oculomotor nerves in Charcot-Marie-Tooth disease 4F We present pathology of the peripheral nerves of a patient with Adult-onset Charcot-Marie-Tooth disease 4F caused by periaxin gene mutation p.D651N. The patient was a 72-year-old woman. She had hoarseness and underwent continuous positive airway pressure therapy at night due to sleep apnea. The patient died abruptly. Remarkable demyelination with tomacula formation was found in the phrenic nerve, vagal nerve, recurrent laryngeal nerve, and oculomotor nerves. The cause of death could have been... pubmed:34993357
A case of Charcot-Marie-Tooth disease type 2S caused by mutation of IGHMBP2 gene Jan 6, 2022 - https://pubmed.ncbi.nlm.nih.gov/34986626/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220106075556&v=2.17.5 A case of Charcot-Marie-Tooth disease type 2S caused by mutation of IGHMBP2 gene No abstract pubmed:34986626
The protective role of mesencephalic astrocyte-derived neurotrophic factor in endoplasmic reticulum stress in RT4-D6P2T schwannoma sells with the S63del MPZ mutation Jan 4, 2022 - Endoplasmic reticulum stress (ERS) occurred in S63del mutant CMT1B mice model, and few drugs has been studied. Mesencephalic astrocyte-derived neurotrophic factor (MANF) can inhibit ERS. This study aimed at investigating the effect of MANF on ERS of RT4-D6P2T schwannoma cells with S63del MPZ Mutation.
An Integrated Approach to Studying Rare Neuromuscular Diseases Using Animal and Human Cell-Based Models Jan 3, 2022 - The necessity of integrating mouse and human models, strategies for accomplishing this integration, and the challenges of doing it at scale are discussed using recently published work detailing the cellular mechanisms underlying GARS-associated CMT as a framework.
Spinal muscular atrophy with predominant lower extremity (SMA-LED) with no signs other than pure motor symptoms at the intersection of multiple overlap syndrome Jan 3, 2022 - https://pubmed.ncbi.nlm.nih.gov/34974950/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220103073756&v=2.17.5 Spinal muscular atrophy with predominant lower extremity (SMA-LED) with no signs other than pure motor symptoms at the intersection of multiple overlap syndrome CONCLUSION: It should be kept in mind that DYNC1H1 mutation, which we are accustomed to seeing with accompanying findings such as orthopedic and ocular dysmorphic findings, sensorineural EMG findings, and intellectual disability, can also observe with pure motor findings such as muscular dystrophy examination findings. pubmed:34974950
O-GlcNAcylation of MORC2 at threonine 556 by OGT couples TGF-β signaling to breast cancer progression Jan 3, 2022 - https://pubmed.ncbi.nlm.nih.gov/34974534/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220103013201&v=2.17.5 O-GlcNAcylation of MORC2 at threonine 556 by OGT couples TGF-β signaling to breast cancer progression MORC family CW-type zinc finger 2 (MORC2) is a newly identified chromatin-remodeling enzyme involved in DNA damage response and gene transcription, and its dysregulation has been linked with Charcot-Marie-Tooth disease, neurodevelopmental disorder, and cancer. Despite its functional importance, how MORC2 is regulated remains enigmatic. Here, we report that MORC2 is O-GlcNAcylated by O-GlcNAc transferase (OGT) at threonine 556. Mutation of this site or pharmacological inhibition of OGT impairs... pubmed:34974534
Prevalence and incidence of neuromuscular conditions in the UK between 2000 and 2019: A retrospective study using primary care data Jan 1, 2022 - https://pubmed.ncbi.nlm.nih.gov/34972157/?utm_source=Other&utm_medium=rss&utm_campaign=None&utm_content=1854v2hhZntSmhEACE68B0jkf9YsWL5KzHFUrhwvQfh3r3hIOk&fc=None&ff=20220101054801&v=2.17.4 Prevalence and incidence of neuromuscular conditions in the UK between 2000 and 2019: A retrospective study using primary care data CONCLUSIONS: Lifetime recording of many NMDs on primary care records exceed current estimates of people living with these conditions; these are important data for health service and care planning. Temporal trends suggest this number is steadily increasing, and while this may partially be due to better recording, it cannot be simply explained by new cases, as incidence remained constant. The increase in prevalence among older ages suggests increases in life expectancy among those living with NMDs... pubmed:34972157