5,232 results match your criteria Charcot-Marie-Tooth Disease

Giant axonal neuropathy: cross sectional analysis of a large natural history cohort.

Brain 2021 Jun 11. Epub 2021 Jun 11.

National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD 20892, USA.

Giant axonal neuropathy (GAN) is an ultra-rare autosomal recessive, progressive neurodegenerative disease with early childhood onset that presents as a prominent sensorimotor neuropathy and commonly progresses to affect both the peripheral nervous system and central nervous system. The disease is caused by biallelic mutations in the GAN gene located on 16q23.2, leading to loss of functional gigaxonin, a substrate specific ubiquitin ligase adapter protein necessary for the regulation of intermediate filament turnover. Read More

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Two cases of DYNC1H1 mutations with intractable epilepsy.

Brain Dev 2021 Jun 3. Epub 2021 Jun 3.

Department of Pediatrics, Jichi Medical University, Tochigi, Japan. Electronic address:

Background: The DYNC1H1 gene encodes the heavy chain of cytoplasmic dynein 1, a core structure of the cytoplasmic dynein complex. Dominant DYNC1H1 mutations are implicated in Charcot-Marie-Tooth disease, axonal, type 20, spinal muscular atrophy, lower extremity-predominant 1, and autosomal dominant mental retardation 13 with neuronal migration defects. We report two patients with DYNC1H1 mutations who had intractable epilepsy and intellectual disability (ID), one with and one without pachygyria. Read More

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A Patient With Kearns Sayre Syndrome and Charcot-Marie-Tooth for Supraventricular Tachycardia Ablation: A Case Report.

A A Pract 2021 Jun 2;15(6):e01488. Epub 2021 Jun 2.

From the Department of Anesthesiology and Perioperative Medicine, University of Missouri, Columbia, Missouri.

Kearns Sayre syndrome (KSS) is a rare mitochondrial myopathy that is associated with progressive impaired ventilatory drive, heart block, and peripheral neuropathy. Charcot-Marie-Tooth disease (CMT) is a rare chronic motor and sensory peripheral neuropathy which includes muscle weakness and restrictive pulmonary impairment. Patients with either condition having anesthesia can have postoperative respiratory failure. Read More

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Clinical and Neuroimaging Features in Charcot-Marie-Tooth Patients with Mutations.

Life (Basel) 2021 May 28;11(6). Epub 2021 May 28.

Departments of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.

Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. Mutations in the gene cause dominant intermediate CMT type F (CMTDIF). The aim of this study is to investigate phenotypic heterogeneities and characteristics of CMT patients with mutations. Read More

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Charcot-Marie-Tooth disease misdiagnosed as chronic inflammatory demyelinating polyradiculoneuropathy: an international multicentric retrospective study.

Eur J Neurol 2021 Jun 1. Epub 2021 Jun 1.

Neurology Department, APHP, CHU de Bicêtre, Le Kremlin-Bicêtre, 94276, France.

Introduction: Charcot-Marie-Tooth (CMT) disease, an untreatable hereditary polyneuropathy, may mimic chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), a treatable neuropathy.

Objective: In this retrospective study, we analyzed the characteristics of CMT patients misdiagnosed as CIDP in 16 University Hospitals from 3 countries, compared these patients with a reference group of CIDP patients, and estimated the cost of misdiagnosis.

Results: Amongst 1104 CIDP cases, we identified 35 CMT patients misdiagnosed as CIDP (3. Read More

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Adeno-associated virus gene therapy to the rescue for Charcot-Marie-Tooth disease type 4J.

John Svaren

J Clin Invest 2021 Jun;131(11)

The genetic peripheral neuropathy known as Charcot-Marie-Tooth disease type 4J (CMT4J) is caused by recessive mutations in the FIG4 gene. The transformational success of adeno-associated virus (AAV) gene therapy for spinal muscular atrophy has generated substantial interest in using this approach to create similar treatments for CMT. In this issue of the JCI, Presa et al. Read More

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Genotype-phenotype correlation in French patients with myelin protein zero gene-related inherited neuropathy.

Eur J Neurol 2021 Jun 1. Epub 2021 Jun 1.

Reference center for neuromuscular disorders and ALS, APHM, CHU La Timone.

Background: Preparations for clinical trials of unfolded protein response (UPR) inhibitors (such as Sephin 1) that target the upregulated UPR in patients with CMT carrying MPZ mutations are currently underway. The inclusion criteria for these trials are still being formulated. Our objective was to characterize the relation between genotypes and phenotypes in patients with CMT caused by MPZ mutations, and to refine the inclusion criteria for future trials. Read More

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Characterization of genotype-phenotype correlation with MORC2 mutated Axonal Charcot-Marie-Tooth disease in a cohort of Chinese patients.

Orphanet J Rare Dis 2021 May 31;16(1):244. Epub 2021 May 31.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Chang Chun Street, Beijing, 100053, People's Republic of China.

Background: Charcot-Marie-Tooth (CMT) disease is an exciting field of study, with a growing number of causal genes and an expanding phenotypic spectrum. The microrchidia family CW-type zinc finger 2 gene (MORC2) was newly identified as a causative gene of CMT2Z in 2016. We aimed to describe the phenotypic-genetic spectrum of MORC2-related diseases in the Chinese population. Read More

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Childhood onset homozygous recessive GDAP1 (p.Pro231Leu) mutation in a 9-year-old puerto rican pediatric female with axonal Charcot-Marie-Tooth disease: A case report.

J Pediatr Rehabil Med 2021 May 23. Epub 2021 May 23.

Physical Medicine and Rehabilitation, University of Puerto Rico School of Medicine, San Juan, Puerto Rico.

Charcot-Marie-Tooth disease (CMT) is a progressive hereditary neuromuscular neuropathy with pathology in the myelin sheath or the axon. CMT caused by mutations in the Ganglioside-induced differentiation associated protein 1 (GDAP1) gene has been described by a spectrum of phenotypic presentations. GDAP1 is a mitochondrial protein responsible for protecting neuronal bodies from oxidative stress. Read More

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Health-related Quality of Life and Satisfaction with German Health Care Services in Patients with Charcot-Marie-Tooth Neuropathy.

Klaus Nagels

J Neuromuscul Dis 2021 May 27. Epub 2021 May 27.

BackgroundCharcot-Marie-Tooth (CMT) neuropathies entail a large group of diseases with different gene mutation patterns, which produce heterogeneous phenotypes. Although health-related quality of life (HRQOL) is significantly impaired, a comprehensive assessment of HRQOL in CMT patients in Germany considering phenotypical heterogeneity represented a research gap.ObjectiveThe aim was to assess HRQOL and the satisfaction with health care in CMT patients in Germany. Read More

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

Aging Cell 2021 May 30:e13391. Epub 2021 May 30.

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

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

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Atypical inflammatory demyelinating syndrome with central and peripheral nerve involvement.

Mult Scler Relat Disord 2021 Mar 26;51:102926. Epub 2021 Mar 26.

Department of Neurology, King's College Hospital, Denmark Hill, London, SE5 9RS.

We report a patient who has peripheral demyelination in the form of chronic inflammatory demyelinating polyneuropathy (CIDP) with central demyelination following a relapsing-remitting disease course. The patient developed bilateral sequential optic neuritis predating the diagnosis of CIPD, then developed a profound brainstem syndrome with ataxia, dysarthria, a complex eye movement disorder, visual disturbance and urinary incontinence. Interval imaging fulfilled McDonald criteria for multiple sclerosis (MS) with a right parieto-occipital tumefactive lesion showing contrast enhancement and new lesions in the right temporal white matter and midbrain tegmentum. Read More

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Prevalence and characterization of pain in patients with Charcot-Marie-Tooth disease type 1A.

Arq Neuropsiquiatr 2021 May 21. Epub 2021 May 21.

Universidade Federal Fluminense, Hospital Universitário Antônio Pedro, Departamento de Neurologia, Niterói RJ, Brasil.

Background: Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common form of hereditary neuropathy.

Objective: To investigate the prevalence and characteristics of pain in patients with CMT1A.

Methods: Nineteen patients with a diagnosis of CMT1A were evaluated between September 2018 and October 2019, and other causes of neuropathy were ruled out. Read More

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Updated review of therapeutic strategies for Charcot-Marie-Tooth disease and related neuropathies.

Expert Rev Neurother 2021 Jun 7:1-13. Epub 2021 Jun 7.

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

: Charcot-Marie-Tooth disease (CMT) and related neuropathies represent the most prevalent inherited neuromuscular disorders. Nonetheless, there is still no pharmacological treatment available for any CMT type. However, the landscape is rapidly evolving and several novel approaches are providing encouraging results in preclinical studies and leading to clinical trials. Read More

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MicroRNAs as Biomarkers of Charcot-Marie-Tooth Disease Type 1A.

Neurology 2021 May 24. Epub 2021 May 24.

Waisman Center and Department of Comparative Biosciences, University of Wisconsin, Madison, WI, USA

Objective: To determine if microRNA's (miR) are elevated in the plasma of individuals affected by the inherited peripheral neuropathy Charcot-Marie-Tooth Disease, type 1A (CMT1A), miR profiling was employed to compare control and CMT1A plasma.

Methods: We performed a screen of CMT1A and control plasma samples to identify miRs that are elevated in CMT1A using next generation sequencing, followed by validation of selected miRs by quantitative PCR, and correlation with protein biomarkers and clinical data: Rash-modified CMT Examination and Neuropathy Scores (CMTES-R and CMTNS-R), ulnar compound muscle action potentials (CMAP), and motor nerve conduction velocities (MNCV).

Results: After an initial pilot screen, a broader screen confirmed elevated levels of several muscle-associated miRNAs (miR1, -133a, -133b, and -206, known as myomiRs) along with a set of miRs that are highly expressed in Schwann cells of peripheral nerve. Read More

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The Longitudinal Early-onset Alzheimer's Disease Study (LEADS): Framework and methodology.

Alzheimers Dement 2021 May 21. Epub 2021 May 21.

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

Patients with early-onset Alzheimer's disease (EOAD) are commonly excluded from large-scale observational and therapeutic studies due to their young age, atypical presentation, or absence of pathogenic mutations. The goals of the Longitudinal EOAD Study (LEADS) are to (1) define the clinical, imaging, and fluid biomarker characteristics of EOAD; (2) develop sensitive cognitive and biomarker measures for future clinical and research use; and (3) establish a trial-ready network. LEADS will follow 400 amyloid beta (Aβ)-positive EOAD, 200 Aβ-negative EOnonAD that meet National Institute on Aging-Alzheimer's Association (NIA-AA) criteria for mild cognitive impairment (MCI) or AD dementia, and 100 age-matched controls. Read More

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Neuropathology of the spinal nerve roots, spinal cord, and brain in the first autopsied case of Charcot-Marie-Tooth disease 4F with a D651N mutation in the periaxin gene.

Neuropathology 2021 May 17. Epub 2021 May 17.

Department of Clinical Laboratory Medicine and Diagnostic Pathology, Shiga University of Medical Science, Ohtsu, Japan.

Charcot-Marie-Tooth disease (CMT) 4F is an autosomal recessive, hereditary peripheral neuropathy, mostly caused by mutations in the periaxin gene (PRX). This article reports neuropathological findings of the spinal nerve roots, spinal cord, and brain of a patient with CMT4F and a D651N missense mutation in PRX. The patient was a 74-year-old woman who had a history of peripheral neuropathy with onset at the age of 30 years. Read More

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Anesthetic Management of A Patient with Charcot-Marie-Tooth Disease for 2-stage Revision of Total Knee Replacement.

Turk J Anaesthesiol Reanim 2021 Apr 1;49(2):178-180. Epub 2021 Apr 1.

Department of Anesthesiology, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Charcot-Marie-Tooth disease is characterised by hereditary motor and sensory neuropathy. Its anaesthetic management is challenging owing to the unpredictable response observed in patients, especially to non-depolarising neuromuscular blocking drugs, and the risk of malignant hyperthermia and cardiorespiratory complications. A 66-year-old woman underwent anaesthesia for 2 different surgical procedures, a 2-stage revision of total knee replacement over a 4-month period. Read More

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A review and analysis of the clinical literature on Charcot-Marie-Tooth disease caused by mutations in neurofilament protein L.

Cytoskeleton (Hoboken) 2021 May 16. Epub 2021 May 16.

Department of Neuroscience, Ohio State University, Columbus, Ohio, USA.

Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neurological disorders and can be caused by mutations in over 100 different genes. One of the causative genes is NEFL on chromosome 8 which encodes neurofilament light protein (NEFL), one of five proteins that co-assemble to form neurofilaments. At least 34 different CMT-causing mutations in NEFL have been reported which span the head, rod, and tail domains of the protein. Read More

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Diabetes coexistent with Charcot-Marie-Tooth disease presenting as a recurrent foot ulcer misdiagnosed as diabetic foot: A case report.

J Diabetes Investig 2021 May 15. Epub 2021 May 15.

Innovation Center for Wound Repair, Diabetic Foot Care Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China.

Both diabetes mellitus and Charcot-Marie-Tooth disease (CMT) can lead to severe peripheral neuropathy. The differential diagnosis of peripheral neuropathy is difficult due to the similar clinical features. There are still some clues, such as unusual muscle atrophy, unmatched severity of peripheral neurogenic damage with nephropathy or retinopathy, which could alert clinicians to make differential diagnosis. Read More

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Early and late manifestations of neuropathy due to HSPB1 mutation in the Jewish Iranian population.

Ann Clin Transl Neurol 2021 Jun 11;8(6):1260-1268. Epub 2021 May 11.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Objective: Mutations in the HSPB1 gene are associated with a distal hereditary motor neuropathy type 2 (dHMN2) or Charcot-Marie-Tooth disease type 2F (CMT2F), usually with autosomal dominant inheritance. This study aimed to describe the phenotype of the HSPB1 c.407G>T (p. Read More

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The Silent Mutation.

Margo A Peyton

JAMA 2021 May;325(17):1721-1722

Johns Hopkins School of Medicine, Baltimore, Maryland.

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Charcot-Marie-Tooth disease type 2F associated with biallelic HSPB1 mutations.

Ann Clin Transl Neurol 2021 May 4;8(5):1158-1164. Epub 2021 May 4.

Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, Neuroscience Section, University of Milan, Milan, Italy.

Objective: This work aims to expand knowledge regarding the genetic spectrum of HSPB1-related diseases. HSPB1 is a gene encoding heat shock protein 27, and mutations in HSPB1 have been identified as the cause of axonal Charcot-Marie-Tooth (CMT) disease type 2F and distal hereditary motor neuropathy (dHMN).

Methods: Two patients with axonal sensorimotor neuropathy underwent detailed clinical examinations, neurophysiological studies, and next-generation sequencing with subsequent bioinformatic prioritization of genetic variants and in silico analysis of the likely causal mutation. Read More

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Glycosylation Limits Forward Trafficking of the Tetraspan Membrane Protein PMP22.

J Biol Chem 2021 Apr 29:100719. Epub 2021 Apr 29.

Department of Biochemistry, Vanderbilt University, Nashville, Tennessee 37240, United States; Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37240, United States. Electronic address:

Peripheral myelin protein 22 (PMP22) folds and trafficks inefficiently, with only 20% of newly expressed protein trafficking to the cell surface. This behavior is exacerbated in many of the mutants associated with Charcot-Marie-Tooth disease (CMTD), motivating further study. Here we characterized the role of N-glycosylation in limiting PMP22 trafficking. Read More

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Next-Generation Sequencing Technologies and Neurogenetic Diseases.

Life (Basel) 2021 Apr 19;11(4). Epub 2021 Apr 19.

Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun 130021, China.

Next-generation sequencing (NGS) technology has led to great advances in understanding the causes of Mendelian and complex neurological diseases. Owing to the complexity of genetic diseases, the genetic factors contributing to many rare and common neurological diseases remain poorly understood. Selecting the correct genetic test based on cost-effectiveness, coverage area, and sequencing range can improve diagnosis, treatments, and prevention. Read More

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Central Alteration in Peripheral Neuropathy of Trembler-J Mice: Hippocampal pmp22 Expression and Behavioral Profile in Anxiety Tests.

Biomolecules 2021 Apr 19;11(4). Epub 2021 Apr 19.

Departamento de Proteínas y Ácidos Nucleicos, Instituto de Investigaciones Biológicas Clemente Estable, 11600 Montevideo, Uruguay.

Charcot-Marie-Tooth (CMT) type 1 disease is the most common human hereditary demyelinating neuropathy. Mutations in pmp22 cause about 70% of all CMT1. Trembler-J (TrJ/+) mice are an animal model of CMT1E, having the same spontaneous pmp22 mutation that is found in humans. Read More

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Management of flexible cavovarus foot in patients with Charcot-Marie-Tooth disease: midterm results.

Rev Esp Cir Ortop Traumatol (Engl Ed) 2021 Apr 24. Epub 2021 Apr 24.

Hospital Universitari i Politècnic La Fe, Valencia, España.

Introduction: Charcot-Marie-Tooth disease (CMT) is a hereditary motor sensory neuropathy that frequently results in a cavovarus foot in the adult. Surgical treatment allows correction of the deformity while preserving an adequate range of motion.

Objective: The objective of this study was to assess the result of posterior tibial tendon transfer, first metatarsal ascent osteotomy, and calcaneal valgus osteotomy in the treatment of cavovarus foot secondary to CMT. Read More

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GDAP1 mutations are frequent among Brazilian patients with autosomal recessive axonal Charcot-Marie-Tooth disease.

Neuromuscul Disord 2021 Mar 20. Epub 2021 Mar 20.

Department of Neurosciences and Behavior Sciences, Ribeirão Preto Medical School, University of São Paulo, Brazil; National Institute of Sciences and Technology - INCT-Translational Medicine - CNPq/FAPESP, São Paulo, Brazil. Electronic address:

Mutations in ganglioside-induced differentiation-associated-protein 1 (GDAP1) are associated with several subtypes of Charcot-Marie-Tooth (CMT) disease, including autosomal recessive and demyelinating (CMT4A); autosomal recessive and axonal (AR-CMT2K); autosomal dominant and axonal (CMT2K); and an intermediate and recessive form (CMTRIA). To date, at least 103 mutations in this gene have been described, but the relative frequency of GDAP1 mutations in the Brazilian CMT population is unknown. In this study, we investigated the frequency of GDAP1 mutations in a cohort of 100 unrelated Brazilian CMT patients. Read More

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The impact of symptoms on daily life as perceived by patients with Charcot-Marie-Tooth type 1A disease.

Neurol Sci 2021 Apr 26. Epub 2021 Apr 26.

Department of Neuroscience, Reproductive and Odontostomatological Science, University of Naples "Federico II", Via Sergio Pansini, 5, 80131, Naples, Italy.

Introduction: In Charcot-Marie-Tooth type 1A (CMT1A) patients, daily life is mainly influenced by mobility and ambulation dysfunctions. The aim of our work was to evaluate the perception of disturbances that mostly impact on daily life in CMT1A patients and its difference on the basis of age, gender, disability, and quality of life.

Methods: Forty-one CMT1A patients underwent neurological assessment focused on establishing clinical disability through the Charcot-Marie-Tooth Neuropathy Score (CMTNS) and quality of life through the Short Form-36 (SF-36) questionnaire. Read More

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