313 results match your criteria Hereditary Neuropathies of the Charcot-Marie-Tooth Disease Type

SIRT2-knockdown rescues GARS-induced Charcot-Marie-Tooth neuropathy.

Aging Cell 2021 06 30;20(6):e13391. Epub 2021 May 30.

State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.

Charcot-Marie-Tooth disease is the most common inherited peripheral neuropathy. Dominant mutations in the glycyl-tRNA synthetase (GARS) gene cause peripheral nerve degeneration and lead to CMT disease type 2D. The underlying mechanisms of mutations in GARS (GARS ) in disease pathogenesis are not fully understood. Read More

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Spinal cord compression from hypertrophic nerve roots in chronic inflammatory demyelinating polyradiculoneuropathy - A case report.

Surg Neurol Int 2021 24;12:114. Epub 2021 Mar 24.

Department of Neurosurgery, Salford Royal NHS Foundation Trust, Greater Manchester, United Kingdom.

Background: Spinal cord compression secondary to nerve root hypertrophy is often attributed to hereditary neuropathies. However, to avoid misdiagnosis, rare immune-mediated neuropathy such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) should not be overlooked. This report presents a case of multilevel nerve root hypertrophy leading to significant cord compression from CIDP. Read More

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A novel PMP22 insertion mutation causing Charcot-Marie-Tooth disease type 3: A case report.

Medicine (Baltimore) 2021 Mar;100(11):e25163

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, China.

Rationale: Charcot-Marie-Tooth disease (CMT) is a group of hereditary neuropathies with clinical features of muscle atrophy, sensory loss, and foot deformities. CMT is related to a number of genes, such as peripheral myelin protein 22 gene (PMP22). Missense mutations, small deletion mutations, and duplications of PMP22 are common in CMT patients, but few insertion mutation cases of PMP22 have been reported. Read More

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Analysis of the conformational changes caused by the mutations in mitofusin2 gene by Insilico approach.

J Pak Med Assoc 2020 Dec;70(12(B)):2342-2345

Department of Zoology, The Women University Multan, Pakistan.

Objective: To find the effect of pathogenic Mitofusin 2 mutations, responsible for Charcot-Marie-Tooth hereditary neuropathy type 2A, on protein structure.

Methods: The study was conducted at department of biosciences COMSATS University Islamabad, Sahiwal campus from September 2016 to July 2017, and comprised patients with Charcot Marie-Tooth hereditary neuropathy type 2A who were divided into early-onset severe group A and late-onset mild group B. Bioinformatics and molecular analysis was done to find the changes in the protein structure caused by the mutation. Read More

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December 2020

New evidence for secondary axonal degeneration in demyelinating neuropathies.

Neurosci Lett 2021 01 24;744:135595. Epub 2020 Dec 24.

Department of Neurology, Neuromuscular Division, Johns Hopkins School of Medicine, Baltimore, MD, United States. Electronic address:

Development of peripheral nervous system (PNS) myelin involves a coordinated series of events between growing axons and the Schwann cell (SC) progenitors that will eventually ensheath them. Myelin sheaths have evolved out of necessity to maintain rapid impulse propagation while accounting for body space constraints. However, myelinating SCs perform additional critical functions that are required to preserve axonal integrity including mitigating energy consumption by establishing the nodal architecture, regulating axon caliber by organizing axonal cytoskeleton networks, providing trophic and potentially metabolic support, possibly supplying genetic translation materials and protecting axons from toxic insults. Read More

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January 2021

The prevalence of hereditary neuromuscular disorders in Northern Norway.

Brain Behav 2021 Jan 13;11(1):e01948. Epub 2020 Nov 13.

National Neuromuscular Centre Norway and Department of Neurology, University Hospital of North Norway, Tromsø, Norway.

Aim: To investigate the point prevalence of hereditary neuromuscular disorders on January 1, 2020 in Northern Norway.

Methods: From January 1, 1999, until January 1, 2020, we screened medical and genetic hospital records in Northern Norway for hereditary neuromuscular disorders.

Results: We identified 542 patients with a hereditary neuromuscular disorder living in Northern Norway, giving a point prevalence of 111. Read More

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January 2021

Demyelinating Charcot-Marie-Tooth neuropathy associated with FBLN5 mutations.

Eur J Neurol 2020 12 5;27(12):2568-2574. Epub 2020 Sep 5.

Department of Orthopaedics and Trauma Surgery, Medical University of Vienna, Vienna, Austria.

Background And Purpose: Charcot-Marie-Tooth disease type 1 (CMT1) is a group of autosomal dominantly inherited demyelinating sensorimotor neuropathies. Symptoms usually start in the first to second decade and include distal muscle weakness and wasting, sensory disturbances and foot deformities. The most frequent cause is a duplication of PMP22 whilst point mutations in PMP22 and other genes are rare causes. Read More

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December 2020

Optimized Protocol to Generate Spinal Motor Neuron Cells from Induced Pluripotent Stem Cells from Charcot Marie Tooth Patients.

Brain Sci 2020 Jun 27;10(7). Epub 2020 Jun 27.

CHU de Limoges, Service de Biochimie et Génétique Moléculaire, F-87000 Limoges, France.

Modelling rare neurogenetic diseases to develop new therapeutic strategies is highly challenging. The use of human-induced pluripotent stem cells (hiPSCs) is a powerful approach to obtain specialized cells from patients. For hereditary peripheral neuropathies, such as Charcot-Marie-Tooth disease (CMT) Type II, spinal motor neurons (MNs) are impaired but are very difficult to study. Read More

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Electrodiagnostic accuracy in polyneuropathies: supervised learning algorithms as a tool for practitioners.

Neurol Sci 2020 Dec 10;41(12):3719-3727. Epub 2020 Jun 10.

Statistics Unit, Department of Economics, University "G. d'Annunzio", Chieti-Pescara, Italy.

Objective: The interpretation of electrophysiological findings may lead to misdiagnosis in polyneuropathies. We investigated the electrodiagnostic accuracy of three supervised learning algorithms (SLAs): shrinkage discriminant analysis, multinomial logistic regression, and support vector machine (SVM), and three expert and three trainee neurophysiologists.

Methods: We enrolled 434 subjects with the following diagnoses: chronic inflammatory demyelinating polyneuropathy (99), Charcot-Marie-Tooth disease type 1A (124), hereditary neuropathy with liability to pressure palsy (46), diabetic polyneuropathy (67), and controls (98). Read More

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December 2020

Subcellular diversion of cholesterol by gain- and loss-of-function mutations in PMP22.

Glia 2020 11 8;68(11):2300-2315. Epub 2020 Jun 8.

Department of Neuroscience, College of Medicine, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA.

Abnormalities of the peripheral myelin protein 22 (PMP22) gene, including duplication, deletion and point mutations are a major culprit in Type 1 Charcot-Marie-Tooth (CMT) diseases. The complete absence of PMP22 alters cholesterol metabolism in Schwann cells, which likely contributes to myelination deficits. Here, we examined the subcellular trafficking of cholesterol in distinct models of PMP22-linked neuropathies. Read More

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November 2020

Novel MTMR2 mutation causing severe Charcot-Marie-Tooth type 4B1 disease: a case report.

Neurogenetics 2020 10 3;21(4):301-304. Epub 2020 Jun 3.

The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.

Mutations in myotubularin-related protein 2 (MTMR2) were shown to underlie Charcot-Marie-Tooth type 4B1 (CMT4B1) disease, a rare autosomal recessive demyelinating neuropathy, characterized by severe early-onset motor and sensory neuropathy. We describe three siblings of consanguineous kindred presenting with hypotonia, reduced muscle tone, action tremor, dysmetria, areflexia, and skeletal deformities, consistent with a diagnosis of CMT. Whole-exome sequencing identified a novel homozygous c. Read More

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October 2020

A 71-nucleotide deletion in the periaxin gene in an Italian patient with late-onset slowly progressive demyelinating Charcot-Marie-Tooth disease.

Eur J Neurol 2020 10;27(10):2109-2110

Institute for Biomedical Research and Innovation, National Research Council (CNR), Mangone (CS), Italy.

Background: Charcot-Marie-Tooth disease (CMT) constitutes a group of heterogeneous hereditary motor and sensor neuropathies. Mutations in the periaxin (PRX) gene cause CMT4F with an autosomal recessive early-onset demyelinating neuropathy and are extremely rare in a non-Romani white population.

Methods: We report on a 66-year-old Italian man presenting with slowly progressive and late-onset demyelinating CMT. Read More

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October 2020

High glucose level as a modifier factor in CMT1A patients.

J Peripher Nerv Syst 2020 06 12;25(2):132-137. Epub 2020 May 12.

Department of Neurosciences and Behavior Sciences, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.

Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common type of hereditary neuropathy worldwide and diabetes mellitus (DM) is the most frequent cause of peripheral neuropathy in the Western world. CMT1A typically manifest as a predominant motor neuropathy, while, DM-related neuropathy often manifests as a predominant sensory disorder. There are some evidences that CMT1A patients that also had DM had a more severe neuropathy. Read More

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Mutations in heat shock protein beta-1 (HSPB1) are associated with a range of clinical phenotypes related to different patterns of motor neuron dysfunction: A case series.

J Neurol Sci 2020 06 27;413:116809. Epub 2020 Mar 27.

Department of Neurology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia; University of Queensland, Centre for Clinical Research, Brisbane, Queensland, Australia.

Background: Heat shock protein beta-1 (HSPB1) is a ubiquitously expressed molecular chaperone that is important in protecting cells against cellular injury. Mutations in this protein are known to cause autosomal dominant hereditary distal axonal neuropathies, including Charcot Marie Tooth disease type 2F (CMT2F) and distal hereditary motor neuropathy (dHMN). However, patients with HSPB1 mutations have also been described with upper motor neuron signs. Read More

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Mutations in HspB1 and hereditary neuropathies.

Cell Stress Chaperones 2020 07 16;25(4):655-665. Epub 2020 Apr 16.

Department of Biochemistry, School of Biology, Moscow State University, Moscow, Russian Federation, 119991.

Charcot-Marie-Tooth (CMT) disease is major hereditary neuropathy. CMT has been linked to mutations in a range of proteins, including the small heat shock protein HspB1. Here we review the properties of several HspB1 mutants associated with CMT. Read More

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[Hereditary Polyneuropathies].

A Ferbert C Roth

Fortschr Neurol Psychiatr 2020 Mar 31;88(3):198-209. Epub 2020 Mar 31.

Hereditary neuropathies are a group of diseases of which the most prevalent is Charcot Marie Tooth disease (CMT). From the clinical point of view pes cavus is a typical yet not specific sign for CMT. Motor signs like bilateral foot drop are dominant over sensory signs. Read More

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Phenotypic convergence in Charcot-Marie-Tooth 2Y with novel VCP mutation.

Neuromuscul Disord 2020 03 7;30(3):232-235. Epub 2020 Feb 7.

McMaster University, Physical Medicine and Neurology, Neuromuscular Disease Clinic, Ontario L8S 4L8, Canada. Electronic address:

Charcot-Marie-Tooth (CMT) disease, a hereditary motor and sensory neuropathy, has subtypes with varied inheritance patterns and phenotypic presentation. Subtypes additionally vary by genetic variants in a number of genes. Pathogenic variants in the VCP gene have newly been associated with CMT type 2. Read More

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Inherited motor-sensory neuropathy with upper limb predominance associated with the tropomyosin-receptor kinase fused gene.

Neuromuscul Disord 2020 03 17;30(3):227-231. Epub 2020 Jan 17.

Section of Medical Genetics, Department of Laboratory Medicine, Telemark Hospital, Skien, Norway.

The Tropomyosin-receptor kinase fused gene (TFG) encodes TFG which is expressed in spinal motor neurons, dorsal root ganglia and cranial nerve nuclei, and plays a role in the dynamics of the endoplasmic reticulum. Two dominant missense TFG mutations have previously been reported in limited geographical areas (Far East, Iran, China) in association with hereditary motor sensory neuropathy with proximal involvement (HMSN-P) of the four limbs, or with Charcot-Marie-Tooth disease type 2 (CMT2). The 60-year-old female proband belonging to a three-generation Italian family presented with an atypical neuropathy characterized by diffuse painful cramps and prominent motor-sensory impairment of the distal upper limbs. Read More

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Clinical and Genetic Features in a Series of Eight Unrelated Patients with Neuropathy Due to Glycyl-tRNA Synthetase (GARS) Variants.

J Neuromuscul Dis 2020 ;7(2):137-143

University Hospitals Bristol NHS Foundation Trust, Bristol, UK.

Pathogenic variants in the Glycyl-tRNA synthetase gene cause the allelic disorders Charcot-Marie-Tooth disease type 2D and distal hereditary motor neuropathy type V. We describe clinical features in 8 unrelated patients found to have Glycyl-tRNA synthetase variants by Next Generation Sequencing. In addition to upper limb predominant symptoms, other presentations included failure to thrive, feeding difficulties and lower limb dominant symptoms. Read More

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November 2020

A de novo EGR2 variant, c.1232A > G p.Asp411Gly, causes severe early-onset Charcot-Marie-Tooth Neuropathy Type 3 (Dejerine-Sottas Neuropathy).

Sci Rep 2019 12 18;9(1):19336. Epub 2019 Dec 18.

Northcott Neuroscience Laboratory, ANZAC Research Institute, Concord, NSW, Australia.

EGR2 (early growth response 2) is a crucial transcription factor for the myelination of the peripheral nervous system. Mutations in EGR2 are reported to cause a heterogenous spectrum of peripheral neuropathy with wide variation in both severity and age of onset, including demyelinating and axonal forms of Charcot-Marie Tooth (CMT) neuropathy, Dejerine-Sottas neuropathy (DSN/CMT3), and congenital hypomyelinating neuropathy (CHN/CMT4E). Here we report a sporadic de novo EGR2 variant, c. Read More

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December 2019

Serum CXCL13 reflects local B-cell mediated inflammatory demyelinating peripheral neuropathy.

Sci Rep 2019 11 11;9(1):16535. Epub 2019 Nov 11.

Peripheral Neuropathy Research Center (PNRC), Dong-A University College of Medicine, Busan, 49201, Republic of Korea.

Immune damages on the peripheral myelin sheath under pro-inflammatory milieu result in primary demyelination in inflammatory demyelinating neuropathy. Inflammatory cytokines implicating in the pathogenesis of inflammatory demyelinating neuropathy have been used for the development of potential biomarkers for the diagnosis of the diseases. In this study, we have found that macrophages, which induce demyelination, expressed a B-cell-recruiting factor CXC chemokine ligand 13 (CXCL13) in mouse and human inflammatory demyelinating nerves. Read More

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November 2019

A Case Report on Charcot-Marie-Tooth Disease with a Novel Periaxin Gene Mutation.

Cureus 2019 Jul 9;11(7):e5111. Epub 2019 Jul 9.

Neurology, University of Missouri, Columbia, USA.

Charcot-Marie-Tooth (CMT) disease is one of the most common primary hereditary neuropathies causing peripheral neuropathies. More than 60 different gene mutations are causing this disease. The gene codes for Periaxin proteins that are expressed by Schwann cells and are necessary for the formation and maintenance of myelination of peripheral nerves. Read More

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Case series: Childhood Charcot-Marie-Tooth: Predominance of axonal subtype.

eNeurologicalSci 2019 Sep 25;16:100200. Epub 2019 Jul 25.

Division of Neurology, Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Case series reports on clinical features of pediatric hereditary neuropathy in Thailand is scarce. Subtype and clinical presentation in childhood-onset CMT differ from adult-onset. The aim of this study is to investigate the CMT phenotype in Thai children. Read More

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September 2019

A neutral lipid-enriched diet improves myelination and alleviates peripheral nerve pathology in neuropathic mice.

Exp Neurol 2019 11 3;321:113031. Epub 2019 Aug 3.

Department of Neuroscience, College of Medicine, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA; Department of Neurology, College of Medicine, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA. Electronic address:

Charcot-Marie-Tooth (CMT) diseases comprise a genetically heterogeneous group of hereditary peripheral neuropathies. Trembler J (TrJ) mice carry a spontaneous mutation in peripheral myelin protein 22 (PMP22) and model early-onset, severe CMT type 1E disease. Recent studies indicate that phospholipid substitution, or cholesterol-enriched diet, benefit myelinated nerves, however such interventions have not been tested in early-onset dysmyelinating neuropathies. Read More

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November 2019

Acute neurotoxicity following vincristine due to Charcot-Marie-Tooth disease in a young child with medulloblastoma.

Neurooncol Pract 2019 May 18;6(3):179-184. Epub 2019 Mar 18.

Department of Pediatrics, Hematology-Oncology, University of Florida, Gainesville.

Vincristine (VCR), a microtubule inhibitor that arrests the cell cycle by blocking metaphase of mitosis, is unique among the vinca alkaloids for causing polyneuropathy. Patients with increased risk of VCR neurotoxicity include the elderly and those with prior history of neuropathy-prone medical conditions. Identifying such risk factors prior to the development of neurotoxicity should be a goal prior to VCR administration. Read More

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Expanding the spectrum of genes responsible for hereditary motor neuropathies.

J Neurol Neurosurg Psychiatry 2019 10 5;90(10):1171-1179. Epub 2019 Jun 5.

Division of Genetics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: Inherited peripheral neuropathies (IPNs) represent a broad group of genetically and clinically heterogeneous disorders, including axonal Charcot-Marie-Tooth type 2 (CMT2) and hereditary motor neuropathy (HMN). Approximately 60%-70% of cases with HMN/CMT2 still remain without a genetic diagnosis. Interestingly, mutations in HMN/CMT2 genes may also be responsible for motor neuron disorders or other neuromuscular diseases, suggesting a broad phenotypic spectrum of clinically and genetically related conditions. Read More

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October 2019

Development of MRC Centre MRI calf muscle fat fraction protocol as a sensitive outcome measure in Hereditary Sensory Neuropathy Type 1.

J Neurol Neurosurg Psychiatry 2019 08 17;90(8):895-906. Epub 2019 Apr 17.

MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK

Objectives: Hereditary sensory neuropathy type 1 (HSN1) is a rare, slowly progressive neuropathy causing profound sensory deficits and often severe motor loss. L-serine supplementation is a possible candidate therapy but the lack of responsive outcome measures is a barrier for undertaking clinical trials in HSN1. We performed a 12-month natural history study to characterise the phenotype of HSN1 and to identify responsive outcome measures. Read More

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A charcot-marie-tooth type 1B kindred associated with hemifacial spasm and trigeminal neuralgia.

Muscle Nerve 2019 07 8;60(1):62-66. Epub 2019 Apr 8.

Dartmouth Hitchcock Medical Center, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.

Introduction: Charcot-Marie-Tooth (CMT) phenotypes can be distinguished by electrophysiology and genetic analysis but few can be identified by their clinical characteristics. Distinctive phenotypes are useful in identifying affected individuals and providing additional clues about the mechanism of the neuropathy. Cranial neuropathies are uncommon features of CMT, and few reports of familial hemifacial spasm (HFS) and trigeminal neuralgia (TN) have been published. Read More

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Charcot-Marie-Tooth disease with pyramidal features due to a new mutation of EGR2 gene.

Acta Biomed 2019 01 24;90(1):104-107. Epub 2019 Jan 24.

Department of Pediatrics, Child Neurology Unit, Santa Maria Nuova Hospital, IRCCS, viale Risorgimento 80, 42123 Reggio Emilia, Italy. Department of Pediatrics, Pediatric Neurophysiology Laboratory, Santa Maria Nuova Hospital, IRCCS, viale Risorgimento 80, 42123 Reggio Emilia, Italy..

Background And Aim Of The Work: Childhood-onset peripheral neuropathies are often of genetic origin. Charcot-Marie-Tooth (CMT), is considered the commonest neuromuscular disorder. Due to its high clinical heterogeneity, especially in the pediatric age, the co-existence of central and peripheral symptoms and signs does not necessarily rule out a diagnosis of hereditary peripheral neuropathy. Read More

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January 2019