4,983 results match your criteria Charcot-Marie-Tooth Disease


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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http://dx.doi.org/10.3390/brainsci10070407DOI Listing

Vagus Nerve Ultrasound in Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Charcot-Marie-Tooth Disease Type 1A.

J Neuroimaging 2020 Jun 27. Epub 2020 Jun 27.

Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Background And Purpose: Both clinical autonomic dysfunction and involvement of autonomic nerves have been reported in a range of peripheral nerve disorders. We employed nerve ultrasound to assess the size of the vagus nerve in a serial study of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Charcot-Marie-Tooth type 1B (CMT1B) as compared to healthy controls (HCs). We correlated these findings with involvement of the median and ulnar nerves. Read More

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http://dx.doi.org/10.1111/jon.12747DOI Listing

C1orf194 deficiency leads to incomplete early embryonic lethality and dominant intermediate Charcot-Marie-Tooth disease in a knockout mouse model.

Hum Mol Genet 2020 Jun 27. Epub 2020 Jun 27.

Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, P.R. China.

Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy, and shows clinical and genetic heterogeneity. Mutations in C1orf194 encoding a Ca2+ regulator in neurons and Schwann cells have been reported previously by us to cause CMT disease. In here, we further investigated the function and pathogenic mechanism of C1or194 by generating C1orf194 knockout (KO) mice. Read More

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http://dx.doi.org/10.1093/hmg/ddaa129DOI Listing

Synergistic PXT3003 therapy uncouples neuromuscular function from dysmyelination in male Charcot-Marie-Tooth disease type 1A (CMT1A) rats.

J Neurosci Res 2020 Jun 26. Epub 2020 Jun 26.

Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany.

Charcot-Marie-Tooth disease 1 A (CMT1A) is caused by an intrachromosomal duplication of the gene encoding for PMP22 leading to peripheral nerve dysmyelination, axonal loss, and progressive muscle weakness. No therapy is available. PXT3003 is a low-dose combination of baclofen, naltrexone, and sorbitol which has been shown to improve disease symptoms in Pmp22 transgenic rats, a bona fide model of CMT1A disease. Read More

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http://dx.doi.org/10.1002/jnr.24679DOI Listing

Confounding clinical presentation and different disease progression in CMT4B1.

Neuromuscul Disord 2020 May 16. Epub 2020 May 16.

APHP, Centre de référence des maladies neuromusculaires, Institut de Myologie, Sorbonne Université, APHP, Hôpital Pitié-Salpêtrière; Paris, France. Electronic address:

We report seven Charcot-Marie-Tooth 4B1 (CMT4B1) patients from four families with distinctive features, presenting with severe distal weakness and cranial nerve involvement. Patient from family 1 presented with congenital varus foot deformity, progressive distal and proximal weakness leading to loss of ambulation at 14 years, bilateral facial palsy and prominent bulbar involvement. In three siblings from family 2, still ambulant in the second decade, neuropathy was associated with marked sweating and Arnold-Chiari syndrome. Read More

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http://dx.doi.org/10.1016/j.nmd.2020.05.003DOI Listing

A video protocol for rapid dissection of mouse dorsal root ganglia from defined spinal levels.

BMC Res Notes 2020 Jun 24;13(1):302. Epub 2020 Jun 24.

Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK.

Objective: Dorsal root ganglia (DRG) are heterogeneous assemblies of assorted sensory neuron cell bodies found in bilateral pairs at every level of the spinal column. Pseudounipolar afferent neurons convert external stimuli from the environment into electrical signals that are retrogradely transmitted to the spinal cord dorsal horn. To do this, they extend single axons from their DRG-resident somas that then bifurcate and project both centrally and distally. Read More

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http://dx.doi.org/10.1186/s13104-020-05147-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313212PMC

Telocytes in the Normal and Pathological Peripheral Nervous System.

Int J Mol Sci 2020 Jun 17;21(12). Epub 2020 Jun 17.

Department of Basic Medical Sciences, Faculty of Medicine, University of La Laguna, 38071 Tenerife, Spain.

We studied telocytes/CD34+ stromal cells in the normal and pathological peripheral nervous system (PNS), for which we reviewed the literature and contributed our observations under light and electron microscopy in this field. We consider the following aspects: (A) general characteristics of telocytes and the terminology used for these cells (e.g. Read More

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http://dx.doi.org/10.3390/ijms21124320DOI Listing

A Yeast-Based Model for Hereditary Motor and Sensory Neuropathies: A Simple System for Complex, Heterogeneous Diseases.

Int J Mol Sci 2020 Jun 16;21(12). Epub 2020 Jun 16.

Neuromuscular Unit, Mossakowski Medical Research Centre Polish Academy of Sciences, 02-106 Warsaw, Poland.

Charcot-Marie-Tooth (CMT) disease encompasses a group of rare disorders that are characterized by similar clinical manifestations and a high genetic heterogeneity. Such excessive diversity presents many problems. Firstly, it makes a proper genetic diagnosis much more difficult and, even when using the most advanced tools, does not guarantee that the cause of the disease will be revealed. Read More

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http://dx.doi.org/10.3390/ijms21124277DOI Listing

Neuropathy-associated histidyl-tRNA synthetase variants attenuate protein synthesis in vitro and disrupt axon outgrowth in developing zebrafish.

FEBS J 2020 Jun 15. Epub 2020 Jun 15.

Department of Biochemistry, University of Vermont, Burlington, United States.

Charcot-Marie-Tooth disease (CMT) encompasses a set of genetically and clinically heterogeneous neuropathies characterized by length dependent dysfunction of the peripheral nervous system. Mutations in over 80 diverse genes are associated with CMT, and aminoacyl-tRNA synthetases (ARS) constitute a large gene family implicated in the disease. Despite considerable efforts to elucidate the mechanistic link between ARS mutations and the CMT phenotype, the molecular basis of the pathology is unknown. Read More

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http://dx.doi.org/10.1111/febs.15449DOI Listing

Hereditary polyneuropathy with optic atrophy due to PDXK variant leading to impaired Vitamin B6 metabolism.

Neuromuscul Disord 2020 Apr 29. Epub 2020 Apr 29.

Institute of Human Genetics, Center for Molecular Medicine Cologne (CMMC), Institute of Genetics, and Center for Rare Diseases Cologne, University of Cologne, Cologne, Germany. Electronic address:

PDXK encodes for a pyridoxal kinase, which converts inactive B vitamers to the active cofactor pyridoxal 5'-phosphate (PLP). Recently, biallelic pathogenic variants in PDXK were shown to cause axonal Charcot-Marie-Tooth disease with optic atrophy that responds to PLP supplementation. We present two affected siblings carrying a novel biallelic missense PDXK variant with a similar phenotype with earlier onset. Read More

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http://dx.doi.org/10.1016/j.nmd.2020.04.004DOI Listing

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

Neurol Sci 2020 Jun 10. 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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http://dx.doi.org/10.1007/s10072-020-04499-yDOI Listing

Peripheral myelin protein 22 preferentially partitions into ordered phase membrane domains.

Proc Natl Acad Sci U S A 2020 Jun 8;117(25):14168-14177. Epub 2020 Jun 8.

Department of Biochemistry, Vanderbilt University, Nashville, TN 37240;

The ordered environment of cholesterol-rich membrane nanodomains is thought to exclude many transmembrane (TM) proteins. Nevertheless, some multispan helical transmembrane proteins have been proposed to partition into these environments. Here, giant plasma membrane vesicles (GPMVs) were employed to quantitatively show that the helical tetraspan peripheral myelin protein 22 (PMP22) exhibits a pronounced preference for, promotes the formation of, and stabilizes ordered membrane domains. Read More

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http://dx.doi.org/10.1073/pnas.2000508117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322011PMC

Validation of the Italian version of the Charcot-Marie-Tooth Health Index.

J Peripher Nerv Syst 2020 Jun 8. Epub 2020 Jun 8.

Unit of Rare Neurodegenerative and Neurometabolic Diseases, Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

The Charcot-Marie-Tooth Health Index (CMT-HI) is a disease-specific patient-reported outcome measure measuring overall disease burden in Charcot-Marie-Tooth (CMT) patients, designed for natural history studies and clinical trials in English-speaking affected individuals. We developed and validated its Italian Charcot-Marie-Tooth Health Index (I-CMT-HI) version. The questionnaire was translated and culturally adapted from source into Italian by two neurologists experienced in CMT and neuromuscular disorders (NMDs). Read More

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http://dx.doi.org/10.1111/jns.12397DOI Listing

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

Glia 2020 Jun 8. 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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http://dx.doi.org/10.1002/glia.23840DOI Listing

Pes cavovarus in Charcot-Marie-Tooth compared to the idiopathic cavovarus foot: A preliminary weightbearing CT analysis.

Foot Ankle Surg 2020 Apr 27. Epub 2020 Apr 27.

Foot and Ankle Unit, Royal National Orthopaedic Hospital, Stanmore, United Kingdom. Electronic address:

Background: Pes cavovarus is a foot deformity that can be idiopathic (I-PC) or acquired secondary to other pathology. Charcot-Marie-Tooth disease (CMT) is the most common adult cause for acquired pes cavovarus deformity (CMT-PC). The foot morphology of these distinct patient groups has not been previously investigated. Read More

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http://dx.doi.org/10.1016/j.fas.2020.04.004DOI Listing

An adapted dance program for children with Charcot-Marie-Tooth disease: An exploratory study.

J Bodyw Mov Ther 2020 Apr 4;24(2):85-91. Epub 2019 Oct 4.

Centre de Réadaptation Marie Enfant, Centre de Recherche du CHU Sainte Justine, Montréal, Canada; Département des Sciences de l'Activité Physique, Université du Québec à Montréal, Montréal, Canada.

Background: Charcot-Marie-Tooth disease (CMT) is a rare hereditary peripheral neuropathy. Its sensorimotor clinical manifestations are heterogeneous, and it might also influence cognitive functions. Physical activity is recommended for adults with CMT, however there is a lack of studies focusing on the effects of physical activity in children with CMT. Read More

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http://dx.doi.org/10.1016/j.jbmt.2019.09.009DOI Listing

Massage therapy treatment and outcomes in a patient with Charcot-Marie-Tooth disease: A case report.

Authors:
Galit Paz

J Bodyw Mov Ther 2020 Apr 25;24(2):130-137. Epub 2019 Oct 25.

Grant MacEwan University, Massage Therapy Program, Canada. Electronic address:

Background: Charcot-Marie-Tooth (CMT) disease, a progressive hereditary peripheral neuropathy, leads to muscle weakness, wasting, and sensory and motor nerve deprivation. The two main types of CMT are CMT1 (demyelinating) and CMT2 (axonal). Initial findings include foot deformities and sensory changes with progression to altered gait, diminished reflexes, and muscle wasting and weakness. Read More

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http://dx.doi.org/10.1016/j.jbmt.2019.10.014DOI Listing

Discovery of 6-Phenylhexanamide Derivatives as Potent Stereoselective Mitofusin Activators for the Treatment of Mitochondrial Diseases.

J Med Chem 2020 Jun 18. Epub 2020 Jun 18.

Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, Missouri 63110, United States.

Mutations in the mitochondrial fusion protein mitofusin (MFN) 2 cause the chronic neurodegenerative condition Charcot-Marie-Tooth disease type 2A (CMT2A), for which there is currently no treatment. Small-molecule activators of MFN1 and MFN2 enhance mitochondrial fusion and offer promise as therapy for this condition, but prototype compounds have poor pharmacokinetic properties. Herein, we describe a rational design of a series of 6-phenylhexanamide derivatives whose pharmacokinetic optimization yielded a 4-hydroxycyclohexyl analogue, , with the potency, selectivity, and oral bioavailability of a preclinical candidate. Read More

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http://dx.doi.org/10.1021/acs.jmedchem.0c00366DOI Listing

Diagnostic yield of targeted sequential and massive panel approaches for inherited neuropathies.

Clin Genet 2020 Jun 7. Epub 2020 Jun 7.

Graduate Program in Medicine, Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

Diagnostic yield of genetic studies for Charcot-Marie-Tooth disease (CMT) is little known, with a lack of epidemiological data to build better diagnostic strategies outside the United States and Europe. We aimed to evaluate the performance of two molecular diagnostic strategies for patients with CMT, and to characterize epidemiological findings of these conditions in southern Brazil. We performed a single-center cross-sectional study, in which 94 patients (55 families) with CMT suspicion were evaluated. Read More

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http://dx.doi.org/10.1111/cge.13793DOI Listing

Pathological mutations in PNKP trigger defects in DNA single-strand break repair but not DNA double-strand break repair.

Nucleic Acids Res 2020 Jun 6. Epub 2020 Jun 6.

Department of Genome Dynamics, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague 4, 142 20, Czech Republic.

Hereditary mutations in polynucleotide kinase-phosphatase (PNKP) result in a spectrum of neurological pathologies ranging from neurodevelopmental dysfunction in microcephaly with early onset seizures (MCSZ) to neurodegeneration in ataxia oculomotor apraxia-4 (AOA4) and Charcot-Marie-Tooth disease (CMT2B2). Consistent with this, PNKP is implicated in the repair of both DNA single-strand breaks (SSBs) and DNA double-strand breaks (DSBs); lesions that can trigger neurodegeneration and neurodevelopmental dysfunction, respectively. Surprisingly, however, we did not detect a significant defect in DSB repair (DSBR) in primary fibroblasts from PNKP patients spanning the spectrum of PNKP-mutated pathologies. Read More

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http://dx.doi.org/10.1093/nar/gkaa489DOI Listing

Whole Exome Sequencing Revealed a Novel GJB1 Pathogenic Variant and a Rare BSCL2 Mutation in Two Iranian Large Pedigrees with Multiple Affected Cases of Charcot-Marie-Tooth.

Int J Mol Cell Med 2019 ;8(3):169-178

Department of Genetics and Molecular Medicine, School of Medicine, Zanjan University of Medical Sciences (ZUMS), Zanjan, Iran.

Charcot-Marie-Tooth disease (CMT) is the most common hereditary neuropathy of the peripheral nervous system with a wide range of severity and age of onset. CMT patients share similar phenotypes which make it often impossible to identify the disease types based on clinical presentation and electrophysiological studies alone. In recent years, novel genetic diagnostic approaches such as whole exome sequencing (WES) has provided a ground for accurate diagnosis of CMT through identification of the disease-causing mutation(s). Read More

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http://dx.doi.org/10.22088/IJMCM.BUMS.8.3.169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241839PMC
January 2019

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

Neurogenetics 2020 Jun 3. 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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http://dx.doi.org/10.1007/s10048-020-00617-2DOI Listing

Psychoacoustics and neurophysiological auditory processing in patients with Charcot-Marie-Tooth disease types 1A and 2A.

Eur J Neurol 2020 Jun 1. Epub 2020 Jun 1.

Department of Otorhinolaryngology, Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background And Purpose: Hidden hearing loss has been reported in patients with Charcot-Marie-Tooth (CMT) disease; however, the auditory-processing deficits have not been widely explored. We investigated the psychoacoustic and neurophysiological aspects of auditory processing in patients with CMT disease type 1A (CMT1A) and type 2A (CMT2A).

Methods: A total of 43 patients with CMT1A and 15 patients with CMT2A were prospectively enrolled. Read More

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http://dx.doi.org/10.1111/ene.14370DOI Listing

A Consensus Statement on the Surgical Treatment of Charcot-Marie-Tooth Disease.

Foot Ankle Int 2020 Jun 1:1071100720922220. Epub 2020 Jun 1.

Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Background: Charcot-Marie-Tooth (CMT) disease is a hereditary motor-sensory neuropathy that is often associated with a cavovarus foot deformity. Limited evidence exists for the orthopedic management of these patients. Our goal was to develop consensus guidelines based upon the clinical experiences and practices of an expert group of foot and ankle surgeons. Read More

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http://dx.doi.org/10.1177/1071100720922220DOI Listing

BAG3 Myopathy Presenting With Prominent Neuropathic Phenotype and No Cardiac or Respiratory Involvement: A Case Report and Literature Review.

J Clin Neuromuscul Dis 2020 Jun;21(4):230-239

Division of Neurology, Department of Pediatrics, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, AR.

Bcl-2-associated athanogene 3 (BAG3) myopathy is a rare myofibrillar myopathy characterized by toe walking and clumsiness in the first decade with rapid progression to cardiomyopathy and restrictive lung disease in the second decade. Most patients (18 patients) have the c.626C >T (p. Read More

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http://dx.doi.org/10.1097/CND.0000000000000300DOI Listing

The formin INF2 in disease: progress from 10 years of research.

Cell Mol Life Sci 2020 May 25. Epub 2020 May 25.

Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain.

Formins are a conserved family of proteins that primarily act to form linear polymers of actin. Despite their importance to the normal functioning of the cytoskeleton, for a long time, the only two formin genes known to be a genetic cause of human disorders were DIAPH1 and DIAPH3, whose mutation causes two distinct forms of hereditary deafness. In the last 10 years, however, the formin INF2 has emerged as an important target of mutations responsible for the appearance of focal segmental glomerulosclerosis, which are histological lesions associated with glomerulus degeneration that often leads to end-stage renal disease. Read More

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http://dx.doi.org/10.1007/s00018-020-03550-7DOI Listing

A Deregulated Stress Response Underlies Distinct INF2-Associated Disease Profiles.

J Am Soc Nephrol 2020 Jun;31(6):1296-1313

Institute of Cell Dynamics and Imaging and Cells in Motion Interfaculty Centre, University of Münster, Münster, Germany

Background: Monogenic diseases provide favorable opportunities to elucidate the molecular mechanisms of disease progression and improve medical diagnostics. However, the complex interplay between genetic and environmental factors in disease etiologies makes it difficult to discern the mechanistic links between different alleles of a single locus and their associated pathophysiologies. Inverted formin 2 (INF2), an actin regulator, mediates a stress response-calcium mediated actin reset, or CaAR-that reorganizes the actin cytoskeleton of mammalian cells in response to calcium influx. Read More

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http://dx.doi.org/10.1681/ASN.2019111174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269351PMC

Optic Neuropathy in Charcot-Marie-Tooth Disease.

J Neuroophthalmol 2020 Apr 16. Epub 2020 Apr 16.

Department of Neurology (AGH, JAW, RAA, SSS), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Translational Center of Excellence for Neuroepidemiology and Neurology Outcomes Research (AGH), University of Pennsylvania, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics (AGH), University of Pennsylvania, Philadelphia, Pennsylvania; Department of Ophthalmology (RAA), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and Division of Ophthalmology (RAA), Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Background: Charcot-Marie-Tooth disease Type 2A (CMT2A) presents with optic atrophy in a subset of patients, but the prevalence and severity of optic nerve involvement in relation to other CMT subtypes has not been explored.

Methods: Patients with genetically confirmed CMT2A (n = 5), CMT1A (n = 9) and CMTX1 (n = 10) underwent high- and low-contrast acuity testing using Sloan letter charts, and circumpapillary retinal nerve fiber layer (RNFL) and macular total retinal, RNFL, and ganglion cell layer/inner plexiform layer thickness was measured using spectral domain optical coherence tomography (OCT). We used age- and gender-adjusted linear regression to compare contrast acuity and retinal thickness between CMT groups. Read More

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http://dx.doi.org/10.1097/WNO.0000000000000965DOI Listing

A novel homozygous variant extending the peripheral myelin protein 22 by 9 amino acids causes early-onset Charcot-Marie-Tooth disease with predominant severe sensory ataxia.

J Peripher Nerv Syst 2020 May 15. Epub 2020 May 15.

Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health & Great Ormond Street Hospital, London, UK.

Peripheral myelin protein 22 (PMP22) related neuropathies account for over 50% of inherited peripheral neuropathies. A gene copy variation results in CMT1A (duplication) and hereditary neuropathy with liability to pressure palsies (HNPP; single deletion). Point mutations comprise both phenotypes. Read More

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http://dx.doi.org/10.1111/jns.12386DOI Listing

Living with a disability during the pandemic. "Instant paper from the field" on rehabilitation answers to the COVID-19 emergency.

Eur J Phys Rehabil Med 2020 May 14. Epub 2020 May 14.

Spinal Unit, Montecatone Rehabilitation Institute, Imola, Bologna, Italy.

COVID-19 pandemic is creating collateral damage to persons with disabling conditions of different aetiology. The restrictions imposed to contain the spread of infection is limiting the access to many health services, including rehabilitation. It is expected that such situation will lead to long lasting negative consequences for persons with disability, increasing functional limitations in chronic conditions and hindering the recovery after acute events. Read More

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http://dx.doi.org/10.23736/S1973-9087.20.06373-XDOI Listing

Pregnancy outcome in Charcot-Marie-Tooth disease: results of the CMT-NET cohort study in Germany.

Eur J Neurol 2020 May 13. Epub 2020 May 13.

Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Aachen, Germany.

Background And Purpose: Systematic research on the effect of Charcot-Marie-Tooth (CMT) disease on the outcome of pregnancy and conversely the effect of pregnancy on neuropathy is still sparse.

Methods: A clinical cohort study and cross-sectional study within the German CMT-NET was conducted between 2016 and 2019. Inclusion criteria were a confirmed diagnosis of CMT and at least one completed pregnancy after 1990. Read More

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http://dx.doi.org/10.1111/ene.14317DOI Listing

Validation of the Italian version of the Charcot-Marie-Tooth disease Pediatric Scale.

J Peripher Nerv Syst 2020 Jun 26;25(2):138-142. Epub 2020 May 26.

University of Sydney School of Health Sciences & Children's Hospital at Westmead, Sydney, New South Wales, Australia.

The Charcot-Marie-Tooth disease Pediatric Scale (CMTPedS) is a Rasch-built clinical outcome measure of disease severity. It is valid, reliable, and responsive to change for children and adolescents aged 3 to 20 years. The aim of this study was to translate and validate an Italian version of the CMTPedS using a validated framework of transcultural adaptation. Read More

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http://dx.doi.org/10.1111/jns.12383DOI Listing

Quantitative assessment of sciatic nerve changes in Charcot-Marie-Tooth type 1A patients using magnetic resonance neurography.

Eur J Neurol 2020 May 11. Epub 2020 May 11.

Neurology Department, APHM, Reference Center for Neuromuscular Diseases and ALS, La Timone University Hospital, Aix-Marseille University, Marseille, France.

Background And Purpose: Nerve tissue alterations have rarely been quantified in Charcot-Marie-Tooth type 1A (CMT1A) patients. The aim of the present study was to quantitatively assess the magnetic resonance imaging (MRI) anomalies of the sciatic and tibial nerves in CMT1A disease using quantitative neurography MRI. It was also intended to seek for correlations with clinical variables. Read More

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http://dx.doi.org/10.1111/ene.14303DOI Listing

Clinical and radiological characterization of novel FIG4-related combined system disease with neuropathy.

Clin Genet 2020 May 8. Epub 2020 May 8.

Paediatric Neurology, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom.

Variants in the FIG4 gene, which encodes a phosphatidylinositol-3,5-bisphosphatase lead to obstruction of endocytic trafficking, causing accumulation of enlarged vesicles in murine peripheral neurons and fibroblasts. Bi-allelic pathogenic variants in FIG4 are associated with neurological disorders including Charcot-Marie-Tooth disease type-4J (CMT4J) and Yunis-Varón syndrome (YVS). We present four probands from three unrelated families, all homozygous for a recurrent FIG4 missense variant c. Read More

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http://dx.doi.org/10.1111/cge.13771DOI Listing

Comprehensive genetic sequence and copy number analysis for Charcot-Marie-Tooth disease in a Canadian cohort of 2517 patients.

J Med Genet 2020 May 6. Epub 2020 May 6.

Molecular Genetics Laboratory, Division of Molecular Diagnostics, London Health Sciences Centre, London, Ontario, Canada

Charcot-Marie-Tooth disease (CMT) is one of the most common Mendelian disorders characterised by genetic heterogeneity, progressive distal muscle weakness and atrophy, foot deformities and distal sensory loss. In this report, we describe genetic testing data including comprehensive sequencing and copy number analysis of 34 CMT-related genes in a Canadian cohort of patients with suspected CMT. We have demonstrated a notable gender testing bias, with an overall diagnostic yield of 15% in males and 21% in females. Read More

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http://dx.doi.org/10.1136/jmedgenet-2019-106641DOI Listing

Pmp22 super-enhancer deletion causes tomacula formation and conduction block in peripheral nerves.

Hum Mol Genet 2020 Jun;29(10):1689-1699

Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA.

Copy number variation of the peripheral nerve myelin gene Peripheral Myelin Protein 22 (PMP22) causes multiple forms of inherited peripheral neuropathy. The duplication of a 1.4 Mb segment surrounding this gene in chromosome 17p12 (c17p12) causes the most common form of Charcot-Marie-Tooth disease type 1A, whereas the reciprocal deletion of this gene causes a separate neuropathy termed hereditary neuropathy with liability to pressure palsies (HNPP). Read More

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http://dx.doi.org/10.1093/hmg/ddaa082DOI Listing
June 2020
6.393 Impact Factor

High glucose level as a modifier factor in CMT1A patients.

J Peripher Nerv Syst 2020 Jun 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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http://dx.doi.org/10.1111/jns.12379DOI Listing

Novel EGR2 variant that associates with Charcot-Marie-Tooth disease when combined with lipopolysaccharide-induced TNF-α factor T49M polymorphism.

Neurol Genet 2020 Apr 3;6(2):e407. Epub 2020 Mar 3.

ISABIAL (FISABIO) (M.E.B.-C., N.P., S.V.-A., A.C.-B., C.D.-M., H.C.), Hospital General Universitario de Alicante; Instituto de Neurociencias de Alicante UMH-CSIC (N.P., S.V.-A., A.C.-B., H.C.), San Juan de Alicante, Spain; Hospital Marina Salud (J.S.-F.), Denia; and Hospital IMED Levante (A.G.-E.), Benidorm, Spain.

Objective: To identify novel genetic mechanisms causing Charcot-Marie-Tooth (CMT) disease.

Methods: We performed a next-generation sequencing study of 34 genes associated with CMT in a patient with peripheral neuropathy.

Results: We found a non-previously described mutation in EGR2 (p. Read More

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http://dx.doi.org/10.1212/NXG.0000000000000407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164973PMC

[Research advance of underlying pathogenesis and target therapies in Charcot-Marie-Tooth disease type 1A].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 May;37(5):578-583

Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.

Charcot-Marie-Tooth disease (CMT) is the commonest form of inherited neuropathy and has an incidence of 1/2500. CMT1A is the commonest subtype of CMT, which is caused by duplication of peripheral myelin protein 22 (PMP22) gene and accounts for approximately 50% of CMT diagnosed by genetic testing. Duplication of PMP22 may influence the production of PMP22 mRNA and protein, and interfere with the proliferation, differentiation and apoptosis of Schwann cells. Read More

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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2020.05.021DOI Listing

Quality of life in hereditary neuropathy with liability to pressure palsies is as impaired as in Charcot-Marie-Tooth disease type 1A.

Acta Neurol Belg 2020 Apr 25. Epub 2020 Apr 25.

Neurology Clinic, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, 6, Dr Subotic Street, 11 000, Belgrade, Serbia.

To date, only one study assessed quality of life (QoL) in patients with hereditary neuropathy with liability to pressure palsies (HNPP). We aimed to fill in this gap by investigating QoL in a cohort of patients with HNPP compared to Charcot-Marie-Tooth type 1A (CMT1A) patients, as well as to analyze sociodemographic and clinical features associated with QoL in HNPP. Eighteen genetically confirmed HNPP patients were age-and gender-matched with 18 CMT1A patients. Read More

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http://dx.doi.org/10.1007/s13760-020-01355-wDOI Listing

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 Jun 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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http://dx.doi.org/10.1016/j.jns.2020.116809DOI Listing

Bi-allelic mutations in HARS1 severely impair histidyl-tRNA synthetase expression and enzymatic activity causing a novel multisystem ataxic syndrome.

Hum Mutat 2020 Jul 29;41(7):1232-1237. Epub 2020 Apr 29.

Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, Pisa, Italy.

Mutations in histidyl-tRNA synthetase (HARS1), an enzyme that charges transfer RNA with the amino acid histidine in the cytoplasm, have only been associated to date with autosomal recessive Usher syndrome type III and autosomal dominant Charcot-Marie-Tooth disease type 2W. Using massive parallel sequencing, we identified bi-allelic HARS1 variants in a child (c.616G>T, p. Read More

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http://dx.doi.org/10.1002/humu.24024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323910PMC

Oxidative Stress, a Crossroad Between Rare Diseases and Neurodegeneration.

Antioxidants (Basel) 2020 Apr 15;9(4). Epub 2020 Apr 15.

Rare Diseases Joint Unit, CIPF-INCLIVA, 46010 Valencia, Spain.

Oxidative stress is an imbalance between production and accumulation of oxygen reactive species and/or reactive nitrogen species in cells and tissues, and the capacity of detoxifying these products, using enzymatic and non-enzymatic components, such as glutathione. Oxidative stress plays roles in several pathological processes in the nervous system, such as neurotoxicity, neuroinflammation, ischemic stroke, and neurodegeneration. The concepts of oxidative stress and rare diseases were formulated in the eighties, and since then, the link between them has not stopped growing. Read More

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http://dx.doi.org/10.3390/antiox9040313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222183PMC

Charcot-Marie-Tooth Type 2B: A New Phenotype Associated with a Novel Mutation and Inhibited EGFR Degradation.

Cells 2020 04 21;9(4). Epub 2020 Apr 21.

Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy.

The rare autosomal dominant Charcot-Marie-Tooth type 2B (CMT2B) is associated with mutations in the gene, involved in the late endocytic pathway. CMT2B is characterized by predominant sensory loss, ulceromutilating features, with lesser-to-absent motor deficits. We characterized clinically and genetically a family harboring a novel pathogenic variant and performed structural and functional analysis of the mutant protein. Read More

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http://dx.doi.org/10.3390/cells9041028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226405PMC

Small heat shock proteins in neurodegenerative diseases.

Cell Stress Chaperones 2020 Apr 22. Epub 2020 Apr 22.

Department of Biomedical Sciences and Institute Born Bunge, Peripheral Neuropathy Research Group, University of Antwerp, Antwerp, Belgium.

Small heat shock proteins are ubiquitously expressed chaperones, yet mutations in some of them cause tissue-specific diseases. Here, we will discuss how small heat shock proteins give rise to neurodegenerative disorders themselves while we will also highlight how these proteins can fulfil protective functions in neurodegenerative disorders caused by protein aggregation. The first half of this paper will be focused on how mutations in HSPB1, HSPB3, and HSPB8 are linked to inherited peripheral neuropathies like Charcot-Marie-Tooth (CMT) disease and distal hereditary motor neuropathy (dHMN). Read More

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http://dx.doi.org/10.1007/s12192-020-01101-4DOI Listing

Phenotypic correlations in a large single-center cohort of patients with BSCL2 nerve disorders: a clinical, neurophysiological and muscle magnetic resonance imaging study.

Eur J Neurol 2020 Apr 22. Epub 2020 Apr 22.

Department of Neurology, Donostia University Hospital, San Sebastian, Spain.

Background And Purpose: BSCL2 heterozygote mutations are a common cause of distal hereditary motor neuropathies (dHMNs). A series of BSCL2 patients is presented and clinical, neurophysiological and muscle magnetic resonance imaging (MRI) findings are correlated.

Methods: Twenty-six patients from five families carrying the p. Read More

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http://dx.doi.org/10.1111/ene.14272DOI Listing
April 2020
4.055 Impact Factor

Genetic spectrum of MCM3AP and its relationship with phenotype of Charcot-Marie-Tooth disease.

J Peripher Nerv Syst 2020 Jun 7;25(2):107-111. Epub 2020 May 7.

Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China.

Mutations in MCM3AP have recently been reported to cause autosomal recessive Charcot-Marie-Tooth disease (CMT). However, only nine CMT families with MCM3AP mutations have been reported and genotype-phenotype correlation remains unclear. This study aimed to investigate the genetic spectrum of MCM3AP and its relationship with phenotype of CMT. Read More

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http://dx.doi.org/10.1111/jns.12377DOI Listing

The suspected SARS-Cov-2 infection in a Charcot-Marie-Tooth patient undergoing postsurgical rehabilitation: the value of telerehabilitation for evaluation and continuing treatment.

Int J Rehabil Res 2020 May 22. Epub 2020 May 22.

Department of neurosciences, rehabilitation, ophthalmology, genetics and maternal/child sciences, University of Genova.

We report, to the best of our knowledge, the first case of a probable COVID-19 infection in a 28-year-old man with Charcot-Marie-Tooth disease. The diagnosis was established through a remote interaction with the patient after early discharge from outpatient therapy due to upcoming traveling restrictions. The COVID-19 disease appeared mild, without major respiratory problems, and no obvious neuromuscular deterioration was reported or observed. Read More

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http://dx.doi.org/10.1097/MRR.0000000000000418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273849PMC