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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

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

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

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

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

Cell Stress Chaperones 2020 Jul 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

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

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

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

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

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

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

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

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

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

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

Institute of Experimental Neurology (InSpe), Division of Neuroscience, IRCCS Ospedale San Raffaele, Milano, Italy

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

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

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

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

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

Mol Neurobiol 2019 Sep 4;56(9):6460-6471. 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

Neurology 2019 01 9;92(4):e359-e370. Epub 2019 Jan 9.

From the Department of Neurology (V.F., W.D., K.W., R.A.-B., A.L.O., F.E.), Biostatistics Center, Department of Medicine (E.A.M.), and Department of Pathology (Neuropathology) (A.L.O.), Massachusetts General Hospital, Harvard Medical School, Boston; Clinical Chemistry (S.S., T.H.), University Hospital Zurich, Switzerland; and University of Massachusetts Medical School (P.N., D.M.-Y., R.B.), Worcester.

Objective: To evaluate the safety and efficacy of l-serine in humans with hereditary sensory autonomic neuropathy type I (HSAN1).

Methods: In this randomized, placebo-controlled, parallel-group trial with open-label extension, patients aged 18-70 years with symptomatic HSAN1 were randomized to l-serine (400 mg/kg/day) or placebo for 1 year. All participants received l-serine during the second year. Read More

J Med Genet 2018 12 10;55(12):814-823. Epub 2018 Nov 10.

Neuromuscular Diseases Unit, Neurology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain.

Background: Mutations in the metalloendopeptidase () gene were initially identified as a cause of autosomal recessive Charcot-Marie-Tooth disease type 2 (CMT2). Subsequently, variants in were linked to other late-onset autosomal dominant polyneuropathies. Thus, our goal was to define the phenotype and mode of inheritance of patients carrying changes in . Read More

Neurosci Res 2019 Feb 24;139:69-78. Epub 2018 Sep 24.

Laboratory of Molecular Neuroscience and Neurology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan; Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo, 157-8535, Japan. Electronic address:

Charcot-Marie-Tooth (CMT) disease is composed of a heterogeneous group of hereditary peripheral neuropathies. The peripheral nervous system primarily comprises two types of cells: neuronal cells and myelinating glial Schwann cells. CMT2 N is an autosomal dominant disease and its responsible gene encodes alanyl-tRNA synthetase (AARS), which is a family of cytoplasmic aminoacyl-tRNA synthetases. Read More

Curr Genomics 2018 Sep;19(6):412-419

Department of Molecular Neuroscience, Institute of Neurology, University College London, London WC1N 3BG, UK.

The rapid development in the last 10-15 years of microarray technologies, such as oligonucleotide array Comparative Genomic Hybridization (CGH) and Single Nucleotide Polymorphisms (SNP) genotyping array, has improved the identification of fine chromosomal structural variants, ranging in length from kilobases (kb) to megabases (Mb), as an important cause of genetic differences among healthy individuals and also as disease-susceptibility and/or disease-causing factors. Structural genomic variations due to unbalanced chromosomal rearrangements are known as Copy-Number Variants (CNVs) and these include variably sized deletions, duplications, triplications and translocations. CNVs can significantly contribute to human diseases and rearrangements in several dosage-sensitive genes have been identified as an important causative mechanism in the molecular aetiology of Charcot-Marie-Tooth (CMT) disease and of several CMT-related disorders, a group of inherited neuropathies with a broad range of clinical phenotypes, inheritance patterns and causative genes. Read More

Neurogenetics 2018 12 24;19(4):215-225. Epub 2018 Jul 24.

Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.

Charcot-Marie-Tooth disease (CMT) represents a heterogeneous group of hereditary peripheral neuropathies. We previously reported a CMT locus on chromosome 19q13.3 segregating with the disease in a large Costa Rican family with axonal neuropathy and autosomal recessive pattern of inheritance (CMT2B2). Read More

Brain 2018 06;141(6):1622-1636

Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

Several genes related to mitochondrial functions have been identified as causative genes of neuropathy or ataxia. Cytochrome c oxidase assembly factor 7 (COA7) may have a role in assembling mitochondrial respiratory chain complexes that function in oxidative phosphorylation. Here we identified four unrelated patients with recessive mutations in COA7 among a Japanese case series of 1396 patients with Charcot-Marie-Tooth disease (CMT) or other inherited peripheral neuropathies, including complex forms of CMT. Read More

Mol Genet Genomic Med 2018 05 23;6(3):422-433. Epub 2018 Mar 23.

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

Inherited peripheral neuropathies (IPNs) are a clinically and genetically heterogeneous group of diseases affecting the motor and sensory peripheral nerves. IPNs have benefited from gene discovery and genetic diagnosis using next-generation sequencing with over 80 causative genes available for testing. Despite this success, up to 50% of cases remain genetically unsolved. Read More

J Peripher Nerv Syst 2018 03 14;23(1):40-48. Epub 2018 Feb 14.

Department of Neurology and Geriatrics, Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

Mutations in small heat shock protein beta-1 (HspB1) have been linked to Charcot-Marie-Tooth (CMT) disease type 2F and distal hereditary motor neuropathy type 2B. Only four cases with HSPB1 mutations have been reported to date in Japan. In this study between April 2007 and October 2014, we conducted gene panel sequencing in a case series of 1,030 patients with inherited peripheral neuropathies (IPNs) using DNA microarray, targeted resequencing, and whole-exome sequencing. Read More

Am J Pathol 2018 03 12;188(3):728-738. Epub 2017 Dec 12.

Department of Neuroscience, College of Medicine, University of Florida, Gainesville, Florida; Department of Neurology, College of Medicine, University of Florida, Gainesville, Florida. Electronic address:

A common form of hereditary autosomal dominant demyelinating neuropathy known as Charcot-Marie-Tooth disease type 1A (CMT1A) is linked with duplication of the peripheral myelin protein 22 (PMP22) gene. Although studies from animal models have led to better understanding of the pathobiology of these neuropathies, there continues to be a gap in the translation of findings from rodents to humans. Because PMP22 was originally identified in fibroblasts as growth arrest specific gene 3 (gas3) and is expressed broadly in the body, it was tested whether skin cells from neuropathic patients would display the cellular pathology observed in Schwann cells from rodent models. Read More

Muscle Nerve 2018 04 24;57(4):664-671. Epub 2017 Oct 24.

Department of Neuroscience, College of Medicine, McKnight Brain Institute, University of Florida, 1149 Newell Drive, Box 100244 Gainesville, Florida, 32610-0244, USA.

Introduction: Patients with hereditary peripheral neuropathies exhibit characteristic deformities of the hands and feet and have difficulty ambulating. To examine to what extent neuropathic animals recapitulate these deficits, we studied trembler J (TrJ) mice, which model early-onset demyelinating neuropathy.

Methods: A cohort of 4-month-old female wild type and neuropathic mice were evaluated for locomotor measurements, neuromuscular function, and skeletal muscle proteolysis and morphometry. Read More

Muscle Nerve 2018 Jan 24;57(1):E18-E23. Epub 2017 Aug 24.

Department of Neurosciences, University of Padova, Padova, Italy.

Introduction: Nerve ultrasound in Charcot-Marie-Tooth (CMT) disease has focused mostly on the upper limbs. We performed an evaluation of a large cohort of CMT patients in which we sonographically characterized nerve abnormalities in different disease types, ages, and nerves.

Methods: Seventy patients affected by different CMT types and hereditary neuropathy with liability to pressure palsies (HNPP) were evaluated, assessing median, ulnar, fibular, tibial, and sural nerves bilaterally. Read More

Hum Mol Genet 2017 09;26(17):3313-3326

Sobell Department of Motor Neuroscience and Movement Disorders.

Mutations in the small heat shock protein Hsp27, encoded by the HSPB1 gene, have been shown to cause Charcot Marie Tooth Disease type 2 (CMT-2) or distal hereditary motor neuropathy (dHMN). Protein aggregation and axonal transport deficits have been implicated in the disease. In this study, we conducted analysis of bidirectional movements of mitochondria in primary motor neuron axons expressing wild type and mutant Hsp27. Read More

Clin Neurol Neurosurg 2017 Apr 13;155:20-21. Epub 2017 Feb 13.

Department of Neurology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany. Electronic address:

Background: Charcot-Marie-Tooth disease (CMT) type 1A is the most common form of CMT 1 and one of the autosomal dominant demyelinating hereditary motor and sensory neuropathies (HMSN). Cranial nerves may be frequently subclinically affected in CMT disease. However manifest clinical signs of cranial nerve involvement are rare. Read More

Eur J Neurol 2017 03;24(3):530-538

Centre de Référence des Maladies Neuromusculaires Paris Est, Institut de Myologie, Hôpital Pitié-Salpêtrière, Paris, France.

Background And Purpose: Charcot-Marie-Tooth (CMT) 1C due to mutations in LITAF/SIMPLE is a rare subtype amongst the autosomal dominant demyelinating forms of CMT. Our objective was to report the clinical and electrophysiological characteristics of 18 CMT1C patients and compare them to 20 patients with PMP22 mutations: 10 CMT1A patients and 10 patients with hereditary neuropathy with liability to pressure palsies (HNPP).

Methods: Charcot-Marie-Tooth 1C patients were followed-up in referral centres for neuromuscular diseases or were identified by familial survey. Read More

Hum Mol Genet 2017 02;26(3):611-623

Department of Biomedical Sciences, University of Padova, Via U. Bassi 58/b 35131 Padova, Italy.

HSJ1 (DNAJB2), a member of the DNAJ family of molecular chaperones, is a key player in neuronal proteostasis maintenance. It binds ubiquitylated proteins through its Ubiquitin Interacting Motifs (UIMs) and facilitates their delivery to the proteasome for degradation. Mutations in the DNAJB2 gene lead to inherited neuropathies such as Charcot-Marie-Tooth type-2, distal hereditary motor neuropathies, spinal muscular atrophy with parkinsonism and the later stages can resemble amyotrophic lateral sclerosis. Read More

J Neuromuscul Dis 2016 05;3(2):183-200

Peripheral Neuropathy Group, VIB Department of Molecular Genetics and Institute Born Bunge, University of Antwerp, Antwerpen, Belgium.

Background: Charcot-Marie-Tooth (CMT) and associated neuropathies, the most common inherited diseases of the peripheral nervous system, remain so far incurable. Three existing murine models of Charcot-Marie-Tooth type 2F (CMT2F) and/or distal hereditary motor neuropathy type IIb (dHMNIIb), caused by mutations in the small heat shock protein B1 gene (HSPB1/HSP27), partially recapitulate the hallmarks of peripheral neuropathy. Because these models overexpress the HSPB1 mutant proteins they differ from the patients' situation. Read More

EMBO Mol Med 2016 12 1;8(12):1438-1454. Epub 2016 Dec 1.

INSPE-Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy.

Charcot-Marie-Tooth (CMT) neuropathies are highly heterogeneous disorders caused by mutations in more than 70 genes, with no available treatment. Thus, it is difficult to envisage a single suitable treatment for all pathogenetic mechanisms. Axonal Neuregulin 1 (Nrg1) type III drives Schwann cell myelination and determines myelin thickness by ErbB2/B3-PI3K-Akt signaling pathway activation. Read More

Exp Neurol 2016 Dec 24;286:40-49. Epub 2016 Aug 24.

Institute of Anatomy and Cell Biology, Department of Molecular Embryology, Albertstraße 17, 79104 Freiburg, Germany. Electronic address:

The human small heat shock proteins (HSPBs) form a family of molecular chaperones comprising ten members (HSPB1-HSPB10), whose functions span from protein quality control to cytoskeletal dynamics and cell death control. Mutations in HSPBs can lead to human disease and particularly point mutations in HSPB1 and HSPB8 are known to lead to peripheral neuropathies. Recently, a missense mutation (R7S) in yet another member of this family, HSPB3, was found to cause an axonal motor neuropathy (distal hereditary motor neuropathy type 2C, dHMN2C). Read More

Cerebellum 2017 04;16(2):599-601

Division of General Neurology and Ataxia Unit, Department of Neurology, Universidade Federal de São Paulo, São Paulo, Brazil.

Herein, we report a patient that presented with late-onset progressive steppage gait, neuropathy and pes cavus, suggesting Charcot-Marie-Tooth (CMT) disease. Subsequent genetic investigation confirmed Friedreich's ataxia (FRDA). We demonstrate that late-onset Friedreich's ataxia (LOFA) may be a CMT mimicker. Read More

Eur J Neurol 2016 10 14;23(10):1566-71. Epub 2016 Jul 14.

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

Background And Purpose: Charcot-Marie-Tooth disease (CMT) type 1A is characterized by uniformly reduced nerve conduction velocity (NCV) that is fully penetrant since the first years of life, remains fairly stable through the life and does not correlate with disability whereas compound muscular action potential (CMAP) amplitude does. The aim of the present study was to analyze the large amount of electrophysiological data collected in the ascorbic acid trial in Italy and the UK (CMT-TRIAAL/CMT-TRAUK) and to use these data to gain insights into the pathophysiology of NCV in CMT1A.

Methods: Baseline electrophysiological data from 271 patients were analysed. Read More

J Peripher Nerv Syst 2016 09;21(3):142-9

Clinic of Central and Peripheral Degenerative Neuropathies Unit, Department of Clinical Neurosciences, IRCCS Foundation, "C. Besta" Neurological Institute, Milan, Italy.

Charcot-Marie-Tooth disease type 4C (CMT4C) is an autosomal recessive (AR) demyelinating neuropathy associated to SH3TC2 mutations, characterized by early onset, spine deformities, and cranial nerve involvement. We screened 43 CMT4 patients (36 index cases) with AR inheritance, demyelinating nerve conductions, and negative testing for PMP22 duplication, GJB1 and MPZ mutations, for SH3TC2 mutations. Twelve patients (11 index cases) had CMT4C as they carried homozygous or compound heterozygous mutations in SH3TC2. Read More

Clin Neurol Neurosurg 2016 May 9;144:67-71. Epub 2016 Mar 9.

Department of Geriatrics, Neurosciences, Head & Neck Surgery and Orthopedics, Institute of Neurology, Catholic University of the Sacred Heart, Rome, Italy; Centro Clinico NEMO, Rome, Italy.

Objectives: CMT is a group of heterogeneous motor and sensory neuropathies divided into demyelinating (CMT1) and axonal forms (CMT2). Distal Hereditary Motor Neuropathy (dHMN) is a motor neuropathy/neuronopathy which resembles CMT. Final genetic diagnosis is poor in CMT2 and in dHMN when compared with CMT1. Read More

J Neuropathol Exp Neurol 2016 Apr 25;75(4):334-46. Epub 2016 Feb 25.

From the Departments of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada.

Mutations in peripheral myelin protein 22 (PMP22) result in the most common form of Charcot-Marie-Tooth (CMT) disease, CMT1A. This hereditary peripheral neuropathy is characterized by dysmyelination of peripheral nerves, reduced nerve conduction velocity, and muscle weakness. APMP22 point mutation in L16P (leucine 16 to proline) underlies a form of human CMT1A as well as the Trembler-J mouse model of CMT1A. Read More

PLoS One 2016 27;11(1):e0147677. Epub 2016 Jan 27.

Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.

Background: A small group of patients with inherited neuropathy that has been shown to be caused by mutations in the BSCL2 gene. However, little information is available about the role of BSCL2 mutations in inherited neuropathies in Taiwan.

Methodology And Principal Findings: Utilizing targeted sequencing, 76 patients with molecularly unassigned Charcot-Marie-Tooth disease type 2 (CMT2) and 8 with distal hereditary motor neuropathy (dHMN), who were selected from 348 unrelated patients with inherited neuropathies, were screened for mutations in the coding regions of BSCL2. Read More

Neural Regen Res 2015 Oct;10(10):1696-9

Department of Neurology, Peking University Third Hospital, Beijing, China.

Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by duplication of the peripheral myelin protein 22 (PMP22) gene on chromosome 17. It is the most common inherited demyelinating neuropathy. Type 2 diabetes mellitus is a common metabolic disorder that frequently causes predominantly sensory neuropathy. Read More

Clin Genet 2016 08 16;90(2):127-33. Epub 2016 Feb 16.

Northcott Neuroscience Laboratory, ANZAC Research Institute, and Sydney Medical School, University of Sydney, Sydney, Australia.

The cytoplasmic dynein-dynactin genes are attractive candidates for neurodegenerative disorders given their functional role in retrograde transport along neurons. The cytoplasmic dynein heavy chain (DYNC1H1) gene has been implicated in various neurodegenerative disorders, and dynactin 1 (DCTN1) genes have been implicated in a wide spectrum of disorders including motor neuron disease, Parkinson's disease, spinobulbar muscular atrophy and hereditary spastic paraplegia. However, the involvement of other dynactin genes with inherited peripheral neuropathies (IPN) namely, hereditary sensory neuropathy, hereditary motor neuropathy and Charcot-Marie-Tooth disease is under reported. Read More

Brain 2016 Jan 10;139(Pt 1):73-85. Epub 2015 Nov 10.

1 Laboratorio di Neurogenetica, CERC - IRCCS Santa Lucia, Rome, Italy 2 Dipartimento di Medicina dei Sistemi, Università di Roma "Tor Vergata", Rome, Italy

Charcot-Marie-Tooth disease is a group of hereditary peripheral neuropathies that share clinical characteristics of progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, as well as diminished tendon reflexes. Hundreds of causative DNA changes have been found, but much of the genetic basis of the disease is still unexplained. Mutations in the ALS5/SPG11/KIAA1840 gene are a frequent cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and peripheral axonal neuropathy, and account for ∼ 40% of autosomal recessive juvenile amyotrophic lateral sclerosis. Read More

Nature 2015 Oct 21;526(7575):710-4. Epub 2015 Oct 21.

Departments of Chemical Physiology and Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.

Selective neuronal loss is a hallmark of neurodegenerative diseases, which, counterintuitively, are often caused by mutations in widely expressed genes. Charcot-Marie-Tooth (CMT) diseases are the most common hereditary peripheral neuropathies, for which there are no effective therapies. A subtype of these diseases--CMT type 2D (CMT2D)--is caused by dominant mutations in GARS, encoding the ubiquitously expressed enzyme glycyl-transfer RNA (tRNA) synthetase (GlyRS). Read More

Clin Chem Lab Med 2016 May;54(5):773-80

Background: Charcot-Marie-Tooth type 1A (CMT1A) is the most common type of hereditary motor and sensory neuropathies (HMSN), caused by the duplication of the 17p11.2 region that includes the PMP22 gene. Reciprocal deletion of the same region is the main cause of hereditary neuropathy with liability to pressure palsies (HNPP). Read More