4,655 results match your criteria Charcot-Marie-Tooth Disease


LRSAM1 variants and founder effect in French families with ataxic form of Charcot-Marie-Tooth type 2.

Eur J Hum Genet 2019 Apr 17. Epub 2019 Apr 17.

AP-HP, G-H Pitié-Salpêtrière, Centre de Référence des Maladies neuromusculaires, Paris Nord/Est/Ile de france, Paris, France.

Currently only 25-30% of patients with axonal forms of Charcot-Marie-Tooth disease (CMT) receive a genetic diagnosis. We aimed to identify the causative gene of CMT type 2 in 8 non-related French families with a distinct clinical phenotype. We collected clinical, electrophysiological, and laboratory findings and performed genetic analyses in four different French laboratories. Read More

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http://dx.doi.org/10.1038/s41431-019-0403-8DOI Listing

A Sporadic Case of Charcot-Marie-Tooth Disease Type 2 with Left Vocal Fold Palsy due to Mitofusin 2 Mutation.

Intern Med 2019 Apr 17. Epub 2019 Apr 17.

Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Japan.

A 33-year-old Japanese woman was referred for hoarseness. She had been diagnosed with Charcot-Marie-Tooth disease at age 3 and bilateral optic atrophy at age 15. Laryngoscopy revealed left vocal fold palsy. Read More

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http://dx.doi.org/10.2169/internalmedicine.2318-18DOI Listing

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 Apr 17. 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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http://dx.doi.org/10.1136/jnnp-2018-320198DOI Listing
April 2019
1 Read

Charcot-Marie-Tooth disease type 2CC due to a frameshift mutation of the neurofilament heavy polypeptide gene in an Austrian family.

Neuromuscul Disord 2019 Feb 20. Epub 2019 Feb 20.

Friedrich-Baur-Institute, Dep. of Neurology, Ludwig-Maximilians-University of Munich, Ziemssenstraße 1A, 80336 Munich, Germany. Electronic address:

Neurofilaments are structural components of motor axons. Recently different variants resulting in translation of a cryptic amyloidogenic element of the neurofilament-heavy polypeptide (NEFH) gene have been described to cause Charcot-Marie-Tooth disease type 2CC (CMT2CC) by forming amyloidogenic toxic protein aggregation. Until now only few CMT2CC patients have been described. Read More

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http://dx.doi.org/10.1016/j.nmd.2019.02.007DOI Listing
February 2019
1 Read

Comparison of three congruent patient-specific cell types for the modelling of a human genetic Schwann-cell disorder.

Nat Biomed Eng 2019 Apr 8. Epub 2019 Apr 8.

Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Patient-specific human-induced pluripotent stem cells (hiPSCs) hold great promise for the modelling of genetic disorders. However, these cells display wide intra- and interindividual variations in gene expression, which makes distinguishing true-positive and false-positive phenotypes challenging. Data from hiPSC phenotypes and human embryonic stem cells (hESCs) harbouring the same disease mutation are also lacking. Read More

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http://dx.doi.org/10.1038/s41551-019-0381-8DOI Listing
April 2019
1 Read

A complex containing lysine-acetylated actin inhibits the formin INF2.

Nat Cell Biol 2019 Apr 8. Epub 2019 Apr 8.

Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.

Inverted formin 2 (INF2) is a member of the formin family of actin assembly factors. Dominant missense mutations in INF2 are linked to two diseases: focal segmental glomerulosclerosis, a kidney disease, and Charcot-Marie-Tooth disease, a neuropathy. All of the disease mutations map to the autoinhibitory diaphanous inhibitory domain. Read More

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http://dx.doi.org/10.1038/s41556-019-0307-4DOI Listing

Modifier Gene Candidates in Charcot-Marie-Tooth Disease Type 1A: A Case-Only Genome-Wide Association Study.

J Neuromuscul Dis 2019 Apr 3. Epub 2019 Apr 3.

Department for Human Genetics and Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.

Background: Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by a uniform 1.5-Mb duplication on chromosome 17p, which includes the PMP22 gene. Patients often present the classic neuropathy phenotype, but also with high clinical variability. Read More

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http://dx.doi.org/10.3233/JND-190377DOI Listing
April 2019
1 Read

Schwann Cell Transcript Biomarkers for Hereditary Neuropathy Skin Biopsies.

Ann Neurol 2019 Apr 4. Epub 2019 Apr 4.

Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA, USA.

Objective: Charcot-Marie-Tooth disease (CMT) is most commonly caused by duplication of a chromosomal segment surrounding Peripheral Myelin Protein 22, or PMP22 gene, which is classified as CMT1A. Several candidate therapies reduce Pmp22 mRNA levels in CMT1A rodent models, but development of biomarkers for clinical trials in CMT1A is a challenge given its slow progression and the difficulty in obtaining nerve samples. Quantitative PCR measurements of PMP22 mRNA in dermal nerves were performed using skin biopsies in human clinical trials for CMT1A, but this approach did not show increased PMP22 mRNA in CMT1A patients compared to controls. Read More

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http://dx.doi.org/10.1002/ana.25480DOI Listing
April 2019
3 Reads

Peripheral Demyelinating Diseases: From Biology to Translational Medicine.

Front Neurol 2019 19;10:87. Epub 2019 Mar 19.

Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.

Demyelinating diseases represent a spectrum of disorders that impose significant burden on global economy and society. Generally, the prognosis of these diseases is poor and there is no available cure. In recent decades, research has shed some light on the biology and physiology of Schwann cells and its neuroprotective effects in the peripheral nervous system (PNS). Read More

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http://dx.doi.org/10.3389/fneur.2019.00087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433847PMC
March 2019
3 Reads

A catalytic domain variant of Mitofusin requiring a wildtype paralog for function uncouples mitochondrial outer-membrane tethering and fusion.

J Biol Chem 2019 Apr 1. Epub 2019 Apr 1.

Biochemistry, University of Washington, United States.

Mitofusins (Mfn) are dynamin-related GTPases that mediate mitochondrial outer membrane fusion, a process that is required for mitochondrial and cellular health. In Mfn1 and Mfn2 paralogs, a conserved phenylalanine (Phe-202) located in the GTPase domain on a conserved beta strand and is part of an aromatic network in the core of this domain. To gain insight into the poorly understood mechanism of Mfn-mediated membrane fusion, here we characterize a Mitofusin mutant variant etiologically linked to Charcot Marie Tooth Syndrome. Read More

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http://dx.doi.org/10.1074/jbc.RA118.006347DOI Listing
April 2019
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NRG1 type I dependent autoparacrine stimulation of Schwann cells in onion bulbs of peripheral neuropathies.

Nat Commun 2019 04 1;10(1):1467. Epub 2019 Apr 1.

Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075, Göttingen, Germany.

In contrast to acute peripheral nerve injury, the molecular response of Schwann cells in chronic neuropathies remains poorly understood. Onion bulb structures are a pathological hallmark of demyelinating neuropathies, but the nature of these formations is unknown. Here, we show that Schwann cells induce the expression of Neuregulin-1 type I (NRG1-I), a paracrine growth factor, in various chronic demyelinating diseases. Read More

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http://dx.doi.org/10.1038/s41467-019-09385-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443727PMC
April 2019
2 Reads
10.742 Impact Factor

iMotor-CNN: Identifying molecular functions of cytoskeleton motor proteins using 2D convolutional neural network via Chou's 5-step rule.

Anal Biochem 2019 Mar 28;575:17-26. Epub 2019 Mar 28.

Medical Humanities Research Cluster, School of Humanities, Nanyang Technological University, 48 Nanyang Ave, 639798, Singapore. Electronic address:

Motor proteins are the driving force behind muscle contraction and are responsible for the active transportation of most proteins and vesicles in the cytoplasm. There are three superfamilies of cytoskeletal motor proteins with various molecular functions and structures: dynein, kinesin, and myosin. The functional loss of a specific motor protein molecular function has linked to a variety of human diseases, e. Read More

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http://dx.doi.org/10.1016/j.ab.2019.03.017DOI Listing
March 2019
2 Reads
2.219 Impact Factor

Are novel outcome measures for Charcot-Marie-Tooth disease sensitive to change? The 6-minute walk test and StepWatch™ Activity Monitor in a 12-month longitudinal study.

Neuromuscul Disord 2019 Apr 2;29(4):310-316. Epub 2019 Feb 2.

Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy; Nemo Sud Clinical Center for Neuromuscular Diseases, Messina, Italy.

Charcot-Marie-Tooth (CMT) is the most common inherited neuropathy, yet has no available pharmacological therapy. Past pharmacotherapy trials failed to provide positive results, possibly due to a poor choice of outcome measures. We previously performed a study in which we validated the 6-minute walk test and StepWatch™ Activity Monitor in CMT. Read More

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http://dx.doi.org/10.1016/j.nmd.2019.01.009DOI Listing
April 2019
1 Read

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

Muscle Nerve 2019 Mar 28. Epub 2019 Mar 28.

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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http://dx.doi.org/10.1002/mus.26478DOI Listing
March 2019
3 Reads

Cost of illness in Charcot-Marie-Tooth neuropathy: Results from Germany.

Neurology 2019 Mar 27. Epub 2019 Mar 27.

From the Institute for Healthcare Management and Health Sciences (E.S., C.K.) and Healthcare Management and Health Services Research (L.G., K.N.), University of Bayreuth; Department of Neurology (S.T., S.K., P.R., M.C.W.), Friedrich-Baur-Institute, Ludwig-Maximilians-University of Munich; and Department of Neurology (O.S.-K.), Hannover Medical School, Germany.

Objective: To assess cost associated with the disease-specific need of patients diagnosed with Charcot-Marie-Tooth neuropathies (CMT) in Germany.

Methods: Patients with CMT were identified through the national patient registry and invited to complete a standardized questionnaire. The data collected include information about health care use, informal care, and other disease-related expenses as well as the working situation. Read More

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http://dx.doi.org/10.1212/WNL.0000000000007376DOI Listing

Enhancing folic acid metabolism suppresses defects associated with loss of Drosophila mitofusin.

Cell Death Dis 2019 Mar 25;10(4):288. Epub 2019 Mar 25.

MRC Toxicology Unit, University of Cambridge, Lancaster Road, Leicester, LE1 9HN, UK.

Mutations in the mitochondrial GTPase mitofusin 2 (MFN2) cause Charcot-Marie-Tooth disease type 2 (CMT2A), a form of peripheral neuropathy that compromises axonal function. Mitofusins promote mitochondrial fusion and regulate mitochondrial dynamics. They are also reported to be involved in forming contacts between mitochondria and the endoplasmic reticulum. Read More

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http://dx.doi.org/10.1038/s41419-019-1496-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433915PMC
March 2019
2 Reads

Low Dose Naltrexone in Dermatology

J Drugs Dermatol 2019 Mar;18(3):235-238

Low-dose naltrexone (LDN) has been successfully studied as an immunomodulatory and anti-inflammatory therapy in a wide range of conditions including Crohn’s disease, fibromyalgia, major depressive disorder, cancer, chronic regional pain syndrome, Charcot-Marie-Tooth, and multiple sclerosis.1-5 Recently, off label LDN has been shown to improve dermatologic conditions such as systemic sclerosis, Hailey-Hailey Disease, lichen planopilaris, and guttate psoriasis.6-9 In this article, we examine the existing evidence for use of LDN in skin disease and discuss its potential application in the treatment of atopic dermatitis (AD). Read More

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March 2019
3 Reads

Gene replacement therapy in a model of Charcot-Marie-Tooth 4C neuropathy.

Brain 2019 Mar 25. Epub 2019 Mar 25.

Neuroscience Laboratory and Neurology Clinics, The Cyprus Institute of Neurology and Genetics and Cyprus School of Molecular Medicine, Nicosia, Cyprus.

Charcot-Marie-Tooth disease type 4C is the most common recessively inherited demyelinating neuropathy that results from loss of function mutations in the SH3TC2 gene. Sh3tc2-/- mice represent a well characterized disease model developing early onset progressive peripheral neuropathy with hypo- and demyelination, slowing of nerve conduction velocities and disturbed nodal architecture. The aim of this project was to develop a gene replacement therapy for treating Charcot-Marie-Tooth disease type 4C to rescue the phenotype of the Sh3tc2-/- mouse model. Read More

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https://academic.oup.com/brain/advance-article/doi/10.1093/b
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http://dx.doi.org/10.1093/brain/awz064DOI Listing
March 2019
6 Reads

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

Acta Biomed 2019 Jan 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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http://dx.doi.org/10.23750/abm.v90i1.6951DOI Listing
January 2019
2 Reads

Phosphoglycerate kinase deficiency: A nationwide multicenter retrospective study.

J Inherit Metab Dis 2019 Mar 19. Epub 2019 Mar 19.

Neurology Department, Hôpital Raymond Poincaré, Paris, France.

Phosphoglycerate kinase (PGK) deficiency is a rare X-linked metabolic disorder caused by mutations in the PGK1 gene. Patients usually develop various combinations of nonspherocytic hemolytic anemia (NSHA), myopathy, and central nervous system disorders. In this national multicenter observational retrospective study, we recorded all known French patients with PGK deficiency, and 3 unrelated patients were identified. Read More

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http://dx.doi.org/10.1002/jimd.12087DOI Listing
March 2019
1 Read

Restoring mitofusin balance prevents axonal degeneration in a Charcot-Marie-Tooth type 2A model.

J Clin Invest 2019 Mar 18;130:1756-1771. Epub 2019 Mar 18.

Center for Neural Science and Medicine, and.

Mitofusin-2 (MFN2) is a mitochondrial outer-membrane protein that plays a pivotal role in mitochondrial dynamics in most tissues, yet mutations in MFN2, which cause Charcot-Marie-Tooth disease type 2A (CMT2A), primarily affect the nervous system. We generated a transgenic mouse model of CMT2A that developed severe early onset vision loss and neurological deficits, axonal degeneration without cell body loss, and cytoplasmic and axonal accumulations of fragmented mitochondria. While mitochondrial aggregates were labeled for mitophagy, mutant MFN2 did not inhibit Parkin-mediated degradation, but instead had a dominant negative effect on mitochondrial fusion only when MFN1 was at low levels, as occurs in neurons. Read More

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http://dx.doi.org/10.1172/JCI124194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436852PMC
March 2019
13 Reads

Finding a new balance to cure Charcot-Marie-Tooth 2A.

J Clin Invest 2019 Mar 18;130:1533-1535. Epub 2019 Mar 18.

Venetian Institute of Molecular Medicine, Padova, Italy.

Motoneurons are particularly sensitive to mutations in mitofusin-2 (MFN2) that cause the neurological disorder Charcot-Marie-Tooth disease type 2A (CMT2A). MFN2 is a mitochondrial outer membrane protein that, together with its homologue MFN1, fuses mitochondria in most tissues. In this issue of the JCI, Zhou and colleagues show that increasing MFN1 expression in neurons can curtail neurological defects in a CMT2A mouse model. Read More

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http://dx.doi.org/10.1172/JCI127820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436877PMC
March 2019
1 Read

Role of Connexin-Based Gap Junction Channels in Communication of Myelin Sheath in Schwann Cells.

Front Cell Neurosci 2019 1;13:69. Epub 2019 Mar 1.

Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago, Chile.

Peripheral nerves have the capacity to conduct action potentials along great distances and quickly recover following damage which is mainly due to Schwann cells (SCs), the most abundant glial cells of the peripheral nervous system (PNS). SCs wrap around an axonal segment multiple times, forming a myelin sheath, allowing for a significant increase in action potential conduction by insulating the axons. Mature myelin consists of compact and non-compact (or cytoplasmic) myelin zones. Read More

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http://dx.doi.org/10.3389/fncel.2019.00069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405416PMC
March 2019
4 Reads

Muscle fat quantification using magnetic resonance imaging: case-control study of Charcot-Marie-Tooth disease patients and volunteers.

J Cachexia Sarcopenia Muscle 2019 Mar 15. Epub 2019 Mar 15.

Department of Radiology, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea.

Background: This study aimed to evaluate the potential value of 3D multiple gradient echo Dixon-based magnetic resonance imaging (MRI) sequence as a tool for thigh intramuscular fat quantification in Charcot-Marie-Tooth disease (CMT) patients.

Methods: A prospective comparison study comprising 18 CMT patients and 18 age/sex-matched volunteers was performed. MRI including 3D multiple gradient echo Dixon-based imaging was performed for each subject. Read More

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http://dx.doi.org/10.1002/jcsm.12415DOI Listing
March 2019
1 Read

Novel GARS mutation presenting as autosomal dominant intermediate Charcot-Marie-Tooth disease: Intermediate or axonal?

J Peripher Nerv Syst 2019 Mar;24(1):161

Service of Clinical Neurophysiology, University Hospital "Marqués de Valdecilla (IDIVAL)", "Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED)", Santander, Spain.

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http://dx.doi.org/10.1111/jns.12300DOI Listing

Community exercise is feasible for neuromuscular diseases and can improve aerobic capacity.

Neurology 2019 Apr 8;92(15):e1773-e1785. Epub 2019 Mar 8.

From Queen Square MRC Centre for Neuromuscular Diseases, Institute of Neurology (A.W., A.P., M.D., P.M.M., M.L., I.S., M.S., M.M.R., M.G.H., G.M.R.), Institute of Sport, Exercise and Health (P.H.), and Department of Statistical Science (G.B.), University College London; National Hospital for Neurology and Neurosurgery (E.D., K.J.), University College Hospitals, NHS Foundation Trust; Faculty of Health, Social Care & Education (M.D., G.M.R.), Kingston University/St George's University of London; Department of Psychology (A.S.), University of Surrey, Guildford; Charcot Marie Tooth United Kingdom (K.B.), Registered Charity Number 1112370; and Movelab (M.T.), Newcastle University, UK.

Objective: The aim of this phase 2 trial was to ascertain the feasibility and effect of community-based aerobic exercise training for people with 2 of the more common neuromuscular diseases: Charcot-Marie-Tooth disease type 1A (CMT) and inclusion body myositis (IBM).

Methods: A randomized single-blinded crossover trial design was used to compare a 12-week aerobic training program using recombinant exercise bicycles compared to a control period. The training occurred 3 times per week in community gyms local to the participants. Read More

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http://dx.doi.org/10.1212/WNL.0000000000007265DOI Listing
April 2019
2 Reads
8.286 Impact Factor

Human 2-Oxoglutarate Dehydrogenase and 2-Oxoadipate Dehydrogenase Both Generate Superoxide/HO in a Side Reaction and Each Could Contribute to Oxidative Stress in Mitochondria.

Neurochem Res 2019 Mar 7. Epub 2019 Mar 7.

Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10641-2304, USA.

According to recent findings, the human 2-oxoglutarate dehydrogenase complex (hOGDHc) could be an important source of the reactive oxygen species in the mitochondria and could contribute to mitochondrial abnormalities associated with multiple neurodegenerative diseases, including Alzheimer's disease, Huntington disease, and Parkinson's disease. The human 2-oxoadipate dehydrogenase (hE1a) is a novel protein, which is encoded by the DHTKD1 gene. Both missence and nonsense mutations were identified in the DHTKD1 that lead to alpha-aminoadipic and alpha-oxoadipic aciduria, a metabolic disorder with a wide variety of the neurological abnormalities, and Charcot-Marie-Tooth disease type 2Q, an inherited neurological disorder affecting the peripheral nervous system. Read More

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http://link.springer.com/10.1007/s11064-019-02765-w
Publisher Site
http://dx.doi.org/10.1007/s11064-019-02765-wDOI Listing
March 2019
3 Reads

Genetic neuromuscular disorders: living the era of a therapeutic revolution. Part 1: peripheral neuropathies.

Neurol Sci 2019 Apr 1;40(4):661-669. Epub 2019 Mar 1.

Unit of Neurology and Neuromuscular Diseases, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.

Recent advances in pathophysiological and genetic mechanisms of some neuromuscular diseases and a rapid progress in new pharmacological technologies led to an accelerated development of innovative treatments, generating an unexpected therapeutic revolution. In part 1, we report already commercially available drugs, just approved drugs and new therapeutic promises in the treatment of peripheral neuropathies. Hereditary transthyretin amyloidosis (hATTR) is a devastating disease due to amyloid accumulation in peripheral nerves, heart and autonomic system. Read More

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http://dx.doi.org/10.1007/s10072-019-03778-7DOI Listing
April 2019
6 Reads

A novel family with axonal Charcot-Marie-Tooth disease caused by a mutation in the EGR2 gene.

J Peripher Nerv Syst 2019 Mar 6. Epub 2019 Mar 6.

Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples "Federico II", Naples, Italy.

EGR2 (Early Growth Response 2) is one of the most important transcription factors involved in myelination in the peripheral nervous system. EGR2 mutations typically cause different forms of demyelinating neuropathy, that is, Charcot-Marie-Tooth type 1D (CMT1D), Dejerine-Sottas Syndrome (DSS), and Congenital Hypomyelinating Neuropathy (CHN). However, the EGR2 gene has been recently associated with an axonal phenotype (CMT2) in a large CMT family. Read More

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http://dx.doi.org/10.1111/jns.12314DOI Listing
March 2019
2 Reads

POLG mutations presenting as Charcot-Marie-Tooth disease.

J Peripher Nerv Syst 2019 Mar 6. Epub 2019 Mar 6.

Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

We report on two patients, with different POLG mutations, in whom axonal neuropathy dominated the clinical picture. One patient presented with late onset sensory axonal neuropathy caused by a homozygous c.2243G>C (p. Read More

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http://dx.doi.org/10.1111/jns.12313DOI Listing

Disease Modeling and Therapeutic Strategies in CMT2A: State of the Art.

Mol Neurobiol 2019 Mar 4. Epub 2019 Mar 4.

Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Via Francesco Sforza 35, 20122, Milan, Italy.

Mitofusin 2 (MFN2) is a protein of the mitochondrial outer membrane that belongs to a family of highly conserved dynamin-related GTPases. It is implicated in several intracellular pathways; however, its main role is the regulation of mitochondrial dynamics, in particular mitochondrial fusion. Mutations in MFN2 are associated with Charcot-Marie-Tooth disease type 2A (CMT2A), a neurological disorder characterized by a wide spectrum of clinical features, primarily a motor sensory neuropathy. Read More

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http://dx.doi.org/10.1007/s12035-019-1533-2DOI Listing
March 2019
4 Reads

LRSAM1 E3 ubiquitin ligase: molecular neurobiological perspectives linked with brain diseases.

Cell Mol Life Sci 2019 Mar 2. Epub 2019 Mar 2.

Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Jodhpur, Rajasthan, 342037, India.

Cellular protein quality control (PQC) plays a significant role in the maintenance of cellular homeostasis. Failure of PQC mechanism may lead to various neurodegenerative diseases due to accumulation of aberrant proteins. To avoid such fatal neuronal conditions PQC employs autophagy and ubiquitin proteasome system (UPS) to degrade misfolded proteins. Read More

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http://dx.doi.org/10.1007/s00018-019-03055-yDOI Listing
March 2019
1 Read

Junctophilins emerge as novel therapeutic targets.

J Cell Physiol 2019 Mar 1. Epub 2019 Mar 1.

Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drugs Study, University of South China, Hengyang, China.

Junctophilins (JPs) emerge to play key role in human pathophysiology. This family includes four subtypes (JP1-4), which are differentially detected in excitable cells. Previous work demonstrated the knockout of JPs that seriously damage physiological functions in skeletal muscle, cardiac, and neurons. Read More

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http://dx.doi.org/10.1002/jcp.28405DOI Listing
March 2019
3 Reads

Generation of induced pluripotent stem cell line, ZJUCHi002-A, from Charcot-Marie-Tooth disease type 2A (CMT2A) patient with a mutation of c.752C>T in MFN2.

Stem Cell Res 2019 Apr 20;36:101411. Epub 2019 Feb 20.

The Children's Hospital Affiliated & Key Laboratory of Diagnosis and Treatment of Neonatal Diseases of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou 310052, China; Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310020, China; Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, School of Medicine, Zhejiang University, Hangzhou 310058, China. Electronic address:

The human induced pluripotent stem cell (iPSC) line ZJUCHi002-A was established from renal epithelial cells present in urine (urinary cells) collected from an 8-year-old Charcot-Marie-Tooth disease type 2A (CMT2A) patient carrying point mutation in MFN2 (c.752C > T). Urinary cells were reprogrammed by retrovirus vectors containing reprogramming factors: OCT4, SOX2, KLF4 and c-MYC. Read More

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http://dx.doi.org/10.1016/j.scr.2019.101411DOI Listing
April 2019
2 Reads
3.693 Impact Factor

Association of SNP in JPH1 gene with severity of disease in Charcot Marie Tooth 2K patients.

J Pak Med Assoc 2019 Feb;69(2):241-243

Department of Zoology, The Women University Multan.

Phenotype varies among the various types of Charcot Marie Tooth Neuropathies(CMT), However the problem arises in cases of same gene but gives a huge variety of phenotype in terms of early and late onset and severity of the disease. To check the impact of rs139723190 SNP on severity of the CMT 2k patients; being a genetic modifier of GDAP1. In the current study CMT 2k patients with early and late onset were analyzed for association of rs139723190 SNP in JPH1 gene responsible for CMT type severe and mild phenotypes. Read More

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February 2019
5 Reads

Aminoacyl-tRNA synthetases and tRNAs in human disease: an introduction to the JBC Reviews thematic series.

J Biol Chem 2019 Apr 24;294(14):5292-5293. Epub 2019 Feb 24.

From the Department of Chemistry and Biochemistry, Center for RNA Biology, and Center for Retroviral Research, The Ohio State University, Columbus, Ohio 43210

Aminoacyl-tRNA synthetases (ARSs) catalyze the attachment of specific amino acids to cognate tRNAs for use in protein synthesis. This historical function of ARSs and tRNAs is fairly well understood. However, ARSs and tRNAs also perform noncanonical functions that are continuing to be unveiled at a rapid pace. Read More

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http://dx.doi.org/10.1074/jbc.REV119.007721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462500PMC

Generation of a human Charcot-Marie-Tooth disease type 1B (CMT1B) iPSC line, ZJUCHi001-A, with a mutation of c.292C>T in MPZ.

Stem Cell Res 2019 Mar 14;35:101407. Epub 2019 Feb 14.

The Children's Hospital Affiliated, Key Laboratory of Diagnosis and Treatment of Neonatal Diseases of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou 310052, China; Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310020, China; Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, School of Medicine, Zhejiang University, Hangzhou 310058, China. Electronic address:

The human iPSC cell line ZJUCHi001-A was established from renal epithelial cells present in urine (urinary cells) harvested from a 2-year-old Charcot-Marie-Tooth disease type 1B (CMT1B) patient carrying point mutation in MPZ (c.292C>T). Urinary cells were reprogrammed by retrovirus vectors containing reprogramming factors: OCT4, SOX2, KLF4 and c-MYC. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S18735061193003
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http://dx.doi.org/10.1016/j.scr.2019.101407DOI Listing
March 2019
7 Reads
3.693 Impact Factor

Clinical and genetic spectrum of sarcoglycanopathies in a large cohort of Chinese patients.

Orphanet J Rare Dis 2019 02 14;14(1):43. Epub 2019 Feb 14.

Department of Neurology, Peking University First Hospital, 8 Xishiku St, Xicheng District, Beijing, 100034, China.

Background: Sarcoglycanopathies comprise four subtypes of autosomal recessive limb-girdle muscular dystrophy (LGMD2C, LGMD2D, LGMD2E, and LGMD2F) that are caused, respectively, by mutations in the SGCG, SGCA, SGCB, and SGCD genes. Knowledge about the clinical and genetic features of sarcoglycanopathies in Chinese patients is limited. The aims of this study were to investigate in detail the clinical manifestations, sarcoglycan expression, and gene mutations in Chinese patients with sarcoglycanopathies and to identify possible correlations between them. Read More

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http://dx.doi.org/10.1186/s13023-019-1021-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376703PMC
February 2019
3 Reads

Cerebral hypomyelination associated with biallelic variants of FIG4.

Hum Mutat 2019 May 28;40(5):619-630. Epub 2019 Feb 28.

Department of Human Genetics, University of Michigan, Ann Arbor, Michigan.

The lipid phosphatase gene FIG4 is responsible for Yunis-Varón syndrome and Charcot-Marie-Tooth disease Type 4J, a peripheral neuropathy. We now describe four families with FIG4 variants and prominent abnormalities of central nervous system (CNS) white matter (leukoencephalopathy), with onset in early childhood, ranging from severe hypomyelination to mild undermyelination, in addition to peripheral neuropathy. Affected individuals inherited biallelic FIG4 variants from heterozygous parents. Read More

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http://doi.wiley.com/10.1002/humu.23720
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http://dx.doi.org/10.1002/humu.23720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467804PMC
May 2019
6 Reads

A network biology approach to unraveling inherited axonopathies.

Sci Rep 2019 Feb 8;9(1):1692. Epub 2019 Feb 8.

Dr. John T. Macdonald Foundation Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.

Inherited axonopathies represent a spectrum of disorders unified by the common pathological mechanism of length-dependent axonal degeneration. Progressive axonal degeneration can lead to both Charcot-Marie-Tooth type 2 (CMT2) and Hereditary Spastic Paraplegia (HSP) depending on the affected neurons: peripheral motor and sensory nerves or central nervous system axons of the corticospinal tract and dorsal columns, respectively. Inherited axonopathies display an extreme degree of genetic heterogeneity of Mendelian high-penetrance genes. Read More

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http://dx.doi.org/10.1038/s41598-018-37119-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368620PMC
February 2019
6 Reads

A network of chaperones prevents and detects failures in membrane protein lipid bilayer integration.

Nat Commun 2019 02 8;10(1):672. Epub 2019 Feb 8.

Center for Integrated Protein Science at the Department of Chemistry, Technical University of Munich, Lichtenbergstr. 4, 85748, Garching, Germany.

A fundamental step in membrane protein biogenesis is their integration into the lipid bilayer with a defined orientation of each transmembrane segment. Despite this, it remains unclear how cells detect and handle failures in this process. Here we show that single point mutations in the membrane protein connexin 32 (Cx32), which cause Charcot-Marie-Tooth disease, can cause failures in membrane integration. Read More

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http://dx.doi.org/10.1038/s41467-019-08632-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368539PMC
February 2019
3 Reads

Deregulation of LRSAM1 expression impairs the levels of TSG101, UBE2N, VPS28, MDM2 and EGFR.

PLoS One 2019 6;14(2):e0211814. Epub 2019 Feb 6.

Neurogenetics Department, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.

CMT is the most common hereditary neuromuscular disorder of the peripheral nervous system with a prevalence of 1/2500 individuals and it is caused by mutations in more than 80 genes. LRSAM1, a RING finger ubiquitin ligase also known as TSG101-associated ligase (TAL), has been associated with Charcot-Marie-Tooth disease type 2P (CMT2P) and to date eight causative mutations have been identified. Little is currently known on the pathogenetic mechanisms that lead to the disease. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211814PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364939PMC
February 2019
1 Read

TRIM2, a novel member of the antiviral family, limits New World arenavirus entry.

PLoS Biol 2019 Feb 6;17(2):e3000137. Epub 2019 Feb 6.

Department of Microbiology and Immunology, UIC College of Medicine, Chicago, Illinois, United States of America.

Tripartite motif (TRIM) proteins belong to a large family with many roles in host biology, including restricting virus infection. Here, we found that TRIM2, which has been implicated in cases of Charcot-Marie-Tooth disease (CMTD) in humans, acts by blocking hemorrhagic fever New World arenavirus (NWA) entry into cells. We show that Trim2-knockout mice, as well as primary fibroblasts from a CMTD patient with mutations in TRIM2, are more highly infected by the NWAs Junín and Tacaribe virus than wild-type mice or cells are. Read More

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http://dx.doi.org/10.1371/journal.pbio.3000137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380604PMC
February 2019
13 Reads

Variation in SIPA1L2 is correlated with phenotype modification in Charcot- Marie- Tooth disease type 1A.

Ann Neurol 2019 Mar;85(3):316-330

Department for Human Genetics and Hussman Institute for Human Genomics, University of Miami, Miami, FL.

Objective: Genetic modifiers in rare disease have long been suspected to contribute to the considerable variance in disease expression, including Charcot-Marie-Tooth disease type 1A (CMT1A). To address this question, the Inherited Neuropathy Consortium collected a large standardized sample of such rare CMT1A patients over a period of 8 years. CMT1A is caused in most patients by a uniformly sized 1. Read More

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http://doi.wiley.com/10.1002/ana.25426
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http://dx.doi.org/10.1002/ana.25426DOI Listing
March 2019
20 Reads
9.977 Impact Factor

[Analysis of gene mutation in a pedigree with autosomal dominant Charcot-Marie-Tooth disease].

Nan Fang Yi Ke Da Xue Xue Bao 2019 Jan;39(1):63-68

Department of Neurology, Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China.

Objective: To investigate the molecular genetic mechanism of Charcot- Marie-Tooth (CMT) disease in a pedigree.

Methods: Genomic DNA was extracted from the peripheral blood of the family members of a pedigree with autosomal dominant CMT disease, and 65 candidate genes of the proband were screened using target exon capture and the next generation sequencing, and the suspicious genes were verified using Sanger sequencing. PolyPhen-2, PROVEAN and SIFT software were used to predict the function of the mutant genes, and PyMOL-1 software was used to simulate the mutant protein structure. Read More

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http://dx.doi.org/10.12122/j.issn.1673-4254.2019.01.10DOI Listing
January 2019
12 Reads

Replication studies of MIR149 association in Charcot-Marie-Tooth disease type 1A in a European population.

Neuromuscul Disord 2019 Feb 25;29(2):160-162. Epub 2018 Dec 25.

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http://dx.doi.org/10.1016/j.nmd.2018.12.012DOI Listing
February 2019
3 Reads

Replication studies of MIR149 association in Charcot-Marie-Tooth disease type 1A in a European population - response.

Neuromuscul Disord 2019 Feb 28;29(2):160-162. Epub 2018 Dec 28.

Department of Biological Sciences, Kongju National University, Gongju, Republic of Korea. Electronic address:

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http://dx.doi.org/10.1016/j.nmd.2018.12.013DOI Listing
February 2019
2 Reads

A cryptic splicing mutation in the INF2 gene causing Charcot-Marie-Tooth disease with minimal glomerular dysfunction.

J Peripher Nerv Syst 2019 Mar 8;24(1):120-124. Epub 2019 Feb 8.

Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Bron, France.

Heterozygous mutations in the inverted formin-2 (INF2) gene provoke focal segmental glomerulosclerosis (FSGS) and intermediate Charcot-Marie-Tooth (CMT) disease with FSGS. Here, we report four patients from a three-generation family with a new cryptic splicing INF2 mutation causing autosomal dominant intermediate CMT with minimal glomerular dysfunction. Three males and one female with a mean age of 51 years (26-87) presented with a slowly progressive sensorimotor polyneuropathy, pes cavus, and kyphoscoliosis. Read More

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http://doi.wiley.com/10.1111/jns.12308
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http://dx.doi.org/10.1111/jns.12308DOI Listing
March 2019
14 Reads

The histone deacetylase class I, II inhibitor trichostatin A delays peripheral neurodegeneration.

J Mol Histol 2019 Apr 22;50(2):167-178. Epub 2019 Jan 22.

Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Kyung Hee, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, South Korea.

Peripheral nerves, which consist of an axon and a unique glial cell called a Schwann cell, transduce signals from the brain and spinal cord to target organs. Peripheral nerve degeneration leads to distal motor or sensory disorders such as diabetic neuropathy, Charcot-Marie-Tooth disease, and Gullain-Barré syndrome, with symptoms such as dysesthesia, speech impairment, vision change, erectile dysfunction, and urinary incontinence. Schwann cells play an important role in peripheral nerve degeneration. Read More

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http://dx.doi.org/10.1007/s10735-019-09815-1DOI Listing
April 2019
6 Reads

Calcium Deregulation and Mitochondrial Bioenergetics in GDAP1-Related CMT Disease.

Int J Mol Sci 2019 Jan 18;20(2). Epub 2019 Jan 18.

Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28029 Madrid, Spain.

The pathology of Charcot-Marie-Tooth (CMT), a disease arising from mutations in different genes, has been associated with an impairment of mitochondrial dynamics and axonal biology of mitochondria. Mutations in () cause several forms of CMT neuropathy, but the pathogenic mechanisms involved remain unclear. GDAP1 is an outer mitochondrial membrane protein highly expressed in neurons. Read More

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http://dx.doi.org/10.3390/ijms20020403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359725PMC
January 2019
1 Read