636 results match your criteria Charcot-Marie-Tooth and Other Hereditary Motor and Sensory Neuropathies


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

Authors:
Galit Paz

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Self-reported physical activity in people with limb-girdle muscular dystrophy and Charcot-Marie-Tooth disease in Norway.

BMC Musculoskelet Disord 2020 Apr 13;21(1):235. Epub 2020 Apr 13.

Institute of Health and Society, University of Oslo, P.O. Box 1089, N-0318, Oslo, Blindern, Norway.

Background: Physical activity is associated with positive health effects, but individuals with neuromuscular disease (NMD) may experience constraints being physically active. There is a gap in the literature on the activity level of people with NMDs, and therefore we did a study to determine the physical activity level in people with Limb-Girdle muscular dystrophy (LGMD) and Charcot-Marie-Tooth disease (CMT).

Methods: This study used a cross-sectional design to obtain self-reported physical activity and sitting time among individuals with LGMD and CMT who were recruited from the Norwegian registry for hereditary and congenital neuromuscular diseases. Read More

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http://dx.doi.org/10.1186/s12891-020-03246-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155285PMC

GARS-related disease in infantile spinal muscular atrophy: Implications for diagnosis and treatment.

Am J Med Genet A 2020 05 17;182(5):1167-1176. Epub 2020 Mar 17.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.

The majority of patients with spinal muscular atrophy (SMA) identified to date harbor a biallelic exonic deletion of SMN1. However, there have been reports of SMA-like disorders that are independent of SMN1, including those due to pathogenic variants in the glycyl-tRNA synthetase gene (GARS1). We report three unrelated patients with de novo variants in GARS1 that are associated with infantile-onset SMA (iSMA). Read More

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http://dx.doi.org/10.1002/ajmg.a.61544DOI Listing

Clinical features of inherited neuropathy with BSCL2 mutations in Japan.

J Peripher Nerv Syst 2020 Jun 12;25(2):125-131. Epub 2020 Mar 12.

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

Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) gene have been reported with different clinical phenotypes including Silver syndrome (SS)/spastic paraplegia 17 (SPG17), distal hereditary motor neuropathy type V (dHMN-V), and Charcot-Marie-Tooth (CMT) disease type 2. We screened 407 Japanese patients who were clinically suspected of having CMT by exome sequencing and searched mutations in BSCL2. As a result, we identified five patients with heterozygous mutations in BSCL2. Read More

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http://dx.doi.org/10.1111/jns.12369DOI Listing

Neuromuscular Mimics of Entrapment Neuropathies of Upper Extremities.

Hand (N Y) 2020 Feb 5:1558944719898801. Epub 2020 Feb 5.

The University of Iowa Carver College of Medicine, Lowa, USA.

Carpal tunnel syndrome and ulnar neuropathy are such common maladies affecting the upper extremties that they often become the default diagnosis when patients complain of numbness, pain, or weakness of the hands. While often correct, there are a number of other conditions that can also cause sensory or motor loss of the hands, which should be considered when appropriate, as they can mimic upper extremity entrapment syndromes. In this review, we will discuss such mimics, including Charcot-Marie-Tooth disease, multifocal motor neuropathy, hereditary neuropathy with pressure palsies, mononeuropathy multiplex, Lewis-Sumner syndrome, brachial plexitis (Parsonage-Turner syndrome), myotonic dystrophy, inclusion body myopathy, and distal myopathy of Welander. Read More

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http://dx.doi.org/10.1177/1558944719898801DOI Listing
February 2020

The first Portuguese family with NEFL-related Charcot-Marie-Tooth type 2 disease.

Acta Myol 2019 Sep 1;38(3):180-183. Epub 2019 Sep 1.

Neuromuscular Disease Unit, Neurology Department, Coimbra University and Hospital Centre, Coimbra, Portugal.

CMT disease caused by gene mutations is rare. The mode of inheritance can be dominant or recessive and nerve conduction velocities can be normal, reduced (demyelinating) or presenting intermediate values. Two Portuguese adult related members in two successive generations were affected by peripheral neuropathy, one with a chronic ataxic peripheral neuropathy and the other with a classical Charcot-Marie-Tooth phenotype. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859411PMC
September 2019

Structural insights of human mitofusin-2 into mitochondrial fusion and CMT2A onset.

Nat Commun 2019 10 29;10(1):4914. Epub 2019 Oct 29.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 510060, Guangzhou, China.

Mitofusin-2 (MFN2) is a dynamin-like GTPase that plays a central role in regulating mitochondrial fusion and cell metabolism. Mutations in MFN2 cause the neurodegenerative disease Charcot-Marie-Tooth type 2A (CMT2A). The molecular basis underlying the physiological and pathological relevance of MFN2 is unclear. Read More

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http://dx.doi.org/10.1038/s41467-019-12912-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820788PMC
October 2019
1 Read

A recurrent GARS mutation causes distal hereditary motor neuropathy.

J Peripher Nerv Syst 2019 12 22;24(4):320-323. Epub 2019 Nov 22.

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

We found a p.Gly327Arg mutation in GARS in two unrelated women, both of whom had a similar phenotype - motor weakness that began in late childhood, distal weakness in the arms and legs, a motor greater than sensory neuropathy with slowing of motor and not sensory conduction velocities. A de novo mutation was proven in one patient and suspected in the other. Read More

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http://dx.doi.org/10.1111/jns.12353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910989PMC
December 2019
2 Reads

Next-generation sequencing in Charcot-Marie-Tooth disease: opportunities and challenges.

Nat Rev Neurol 2019 11 3;15(11):644-656. Epub 2019 Oct 3.

MRC Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.

Charcot-Marie-Tooth disease and the related disorders hereditary motor neuropathy and hereditary sensory neuropathy, collectively termed CMT, are the commonest group of inherited neuromuscular diseases, and they exhibit wide phenotypic and genetic heterogeneity. CMT is usually characterized by distal muscle atrophy, often with foot deformity, weakness and sensory loss. In the past decade, next-generation sequencing (NGS) technologies have revolutionized genomic medicine and, as these technologies are being applied to clinical practice, they are changing our diagnostic approach to CMT. Read More

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http://dx.doi.org/10.1038/s41582-019-0254-5DOI Listing
November 2019
1 Read

CMT disease severity correlates with mutation-induced open conformation of histidyl-tRNA synthetase, not aminoacylation loss, in patient cells.

Proc Natl Acad Sci U S A 2019 09 9;116(39):19440-19448. Epub 2019 Sep 9.

Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037;

Aminoacyl-transfer RNA (tRNA) synthetases (aaRSs) are the largest protein family causatively linked to neurodegenerative Charcot-Marie-Tooth (CMT) disease. Dominant mutations cause the disease, and studies of CMT disease-causing mutant glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase (TyrRS) showed their mutations create neomorphic structures consistent with a gain-of-function mechanism. In contrast, based on a yeast model, loss of aminoacylation function was reported for CMT disease mutants in histidyl-tRNA synthetase (HisRS). Read More

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http://dx.doi.org/10.1073/pnas.1908288116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765236PMC
September 2019
3 Reads

Nerve size correlates with clinical severity in Charcot-Marie-Tooth disease 1A.

Muscle Nerve 2019 12 10;60(6):744-748. Epub 2019 Sep 10.

Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.

Introduction: Nerve cross-sectional area (CSA) is larger than normal in Charcot-Marie-Tooth disease 1A (CMT1A), although to a variable extent. We explored whether CSA is correlated with CMT clinical severity measured with neuropathy score version 2 (CMTNS2) and its examination subscore (CMTES2) in CMT1A.

Methods: We assessed 56 patients with CMT1A (42 families). Read More

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http://dx.doi.org/10.1002/mus.26688DOI Listing
December 2019
4 Reads
2.283 Impact Factor

A special association between Charcot-Marie-Tooth type 1A disease and relapsing remitting multiple sclerosis.

Mult Scler Relat Disord 2019 Oct 22;35:83-85. Epub 2019 Jul 22.

Hacettepe University Medical School, Department of Physical and Rehabilitation Medicine, Ankara, Turkey.

Background: Central nervous system involvement has been reported in different subtypes of Charcot-Marie-Tooth (CMT) diseases. The increasing number of cases with CMT and MS may provide further information about the common pathway of demyelination and MS pathogenesis.

Case Presentation: We report the case of a 21-year-old woman with CMT1A and MS. Read More

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http://dx.doi.org/10.1016/j.msard.2019.07.015DOI Listing
October 2019
2 Reads

Charcot-Marie-Tooth disease and related disorders: an evolving landscape.

Curr Opin Neurol 2019 10;32(5):641-650

MRC Centre for Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.

Purpose Of Review: Charcot-Marie-Tooth (CMT) disease and related disorders are the commonest group of inherited neuromuscular diseases and represent a heterogeneous group of disorders. This review will cover recent advances in genetic diagnosis and the evolving genetic and phenotype landscape of this disease group. We will review recent evidence of the increasingly recognized phenotypic overlap with other neurodegenerative conditions including hereditary spastic paraplegia, hereditary ataxias and mitochondrial diseases and highlight the importance of deep phenotyping to inform genetic diagnosis and prognosis. Read More

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http://dx.doi.org/10.1097/WCO.0000000000000735DOI Listing
October 2019
2 Reads

Severe Consequences of SAC3/FIG4 Phosphatase Deficiency to Phosphoinositides in Patients with Charcot-Marie-Tooth Disease Type-4J.

Mol Neurobiol 2019 Dec 16;56(12):8656-8667. Epub 2019 Jul 16.

Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA.

Charcot-Marie-Tooth disease type-4J (CMT4J), an autosomal recessively inherited peripheral neuropathy characterized by neuronal degeneration, segmental demyelination, and limb muscle weakness, is caused by compound heterozygous mutations in the SAC3/FIG4 gene, resulting in SAC3/FIG4 protein deficiency. SAC3/FIG4 is a phosphatase that not only turns over PtdIns(3,5)P to PtdIns3P but also promotes PtdIns(3,5)P synthesis by activating the PIKFYVE kinase that also makes PtdIns5P. Whether CMT4J patients have alterations in PtdIns(3,5)P, PtdIns5P or in other phosphoinositides (PIs), and if yes, in what direction these changes might be, has never been examined. Read More

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http://dx.doi.org/10.1007/s12035-019-01693-8DOI Listing
December 2019
2 Reads
5.137 Impact Factor

Compound heterozygous mutations of SH3TC2 in Charcot-Marie-Tooth disease type 4C patients.

J Hum Genet 2019 Sep 21;64(9):961-965. Epub 2019 Jun 21.

Department of Biological Sciences, Kongju National University, 56 Gongjudaehak-ro, Gongju, 32588, Korea.

Charcot-Marie-Tooth disease type 4C (CMT4C) is an autosomal recessive neuropathy caused by SH3TC2 mutations, characterized by spine deformities and cranial nerve involvement. This study identified four CMT4C families with compound heterozygous SH3TC2 mutations from 504 Korean demyelinating or intermediate CMT patients. The frequency of the CMT4C was calculated as 0. Read More

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http://dx.doi.org/10.1038/s10038-019-0636-yDOI Listing
September 2019
5 Reads
2.462 Impact Factor

Whole exome sequencing revealed a novel dystrophin-related protein-2 () deletion in an Iranian family with symptoms of polyneuropathy.

Iran J Basic Med Sci 2019 May;22(5):576-580

Aboozar Children's Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Objectives: Charcot-Marie Tooth disease (CMT) is one of the main inherited causes of motor and sensory neuropathies with variable expressivity and age-of onset. Although more than 70 genes have been identified for CMT, more studies are needed to discover other genes involved in CMT. Introduction of whole exome sequencing (WES) to capture all the exons may help to find these genes. Read More

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http://dx.doi.org/10.22038/ijbms.2019.30754.7414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556509PMC
May 2019
7 Reads

Charcot-Marie-Tooth 2F (Hsp27 mutations): A review.

Neurobiol Dis 2019 10 15;130:104505. Epub 2019 Jun 15.

Health Science Center, L-15, 023, Stony Brook University Medical Center, Stony Brook, NY 11794-8430, United States of America. Electronic address:

Charcot-Marie-Tooth disease is a commonly inherited form of neuropathy. Although named over 100 years ago, identification of subtypes of Charcot-Marie-Tooth has rapidly expanded in the preceding decades with the advancement of genetic sequencing, including type 2F (CMT2F), due to mutations in heat shock protein 27 (Hsp27). However, despite CMT being one of the most common inherited neurological diseases, definitive mechanistic models of pathology and effective treatments for CMT2F are lacking. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.104505DOI Listing
October 2019
23 Reads

Mutation spectrum of Charcot-Marie-Tooth disease among the Han Chinese in Taiwan.

Ann Clin Transl Neurol 2019 Jun 27;6(6):1090-1101. Epub 2019 May 27.

Neurological Institute, Taipei Veterans General Hospital Taipei Taiwan.

Objective: Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous group of inherited neuropathies. Mutations in more than 90 genes have been implicated in CMT; however, the mutational spectrum of CMT in Chinese population remains obscure. This study aims to provide a comprehensive overview of the frequency of mutations in Taiwanese patients with CMT and look for genotype-phenotype correlations. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/acn3.50797
Publisher Site
http://dx.doi.org/10.1002/acn3.50797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562034PMC
June 2019
12 Reads

A novel mutation in the GARS gene in a Malian family with Charcot-Marie-Tooth disease.

Mol Genet Genomic Med 2019 07 7;7(7):e00782. Epub 2019 Jun 7.

Faculté de Médecine et d'Odontostomatologie, USTTB, Bamako, Mali.

Background: Charcot-Marie-Tooth (CMT) disease is a very heterogeneous neurological condition with more than 90 reported genetic entities. It is the most common inherited peripheral neuropathy; however, cases are rarely reported in sub-Saharan Africa. In addition, only few families, mostly of Caucasian ancestry, have been reported to have Charcot-Marie-Tooth disease type 2D (CMT2D) mutations. Read More

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http://dx.doi.org/10.1002/mgg3.782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625146PMC
July 2019
4 Reads

Expanding the spectrum of genes responsible for hereditary motor neuropathies.

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

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

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http://dx.doi.org/10.1136/jnnp-2019-320717DOI Listing
October 2019
30 Reads

A painful foot with diagnostic and therapeutic consequences.

Scand J Pain 2019 07;19(3):615-618

Unit for Congenital and Hereditary Neuromuscular Conditions (EMAN), Department of Neurology, Oslo University Hospital, Oslo, Norway.

Background A wide range of patients are referred to multidisciplinary pain clinics. An important part of the work-up is a thorough pain analysis that might reveal a specific cause for chronic pain. Method We describe a patient with chronic pain in one foot after a light trauma and repeated surgery. Read More

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http://dx.doi.org/10.1515/sjpain-2019-0015DOI Listing

Continuum of phenotypes in hereditary motor and sensory neuropathy with proximal predominance and Charcot-Marie-Tooth patients with TFG mutation.

Am J Med Genet A 2019 08 20;179(8):1507-1515. Epub 2019 May 20.

School of Biology, College of Science, University of Tehran, Tehran, Iran.

Charcot-Marie-Tooth (CMT) is a common neuropathy, and hereditary motor and sensory neuropathy with proximal predominance (HMSN-P) is a recently described rare neuromuscular disease. Although many genes have been implicated for CMT, TFG is the only known HMSN-P-causing gene. Within the framework of diagnostic criteria, clinical variation is evident among CMT-diagnosed and also HMSN-P-diagnosed individuals. Read More

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http://dx.doi.org/10.1002/ajmg.a.61184DOI Listing
August 2019
25 Reads
2.159 Impact Factor

Whole genome sequencing reveals novel IGHMBP2 variant leading to unique cryptic splice-site and Charcot-Marie-Tooth phenotype with early onset symptoms.

Mol Genet Genomic Med 2019 06 25;7(6):e00676. Epub 2019 Apr 25.

Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.

Background: Rare variants (RV) in immunoglobulin mu-binding protein 2 (IGHMBP2) [OMIM 600502] can cause an autosomal recessive type of Charcot-Marie-Tooth (CMT) disease [OMIM 616155], an inherited peripheral neuropathy. Over 40 different genes are associated with CMT, with different possible inheritance patterns.

Methods And Results: An 11-year-old female with motor delays was found to have distal atrophy, weakness, and areflexia without bulbar or sensory findings. Read More

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http://dx.doi.org/10.1002/mgg3.676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565564PMC
June 2019
10 Reads

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

Nat Cell Biol 2019 05 8;21(5):592-602. 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501848PMC
May 2019
5 Reads

Schwann cell transcript biomarkers for hereditary neuropathy skin biopsies.

Ann Neurol 2019 06 22;85(6):887-898. Epub 2019 Apr 22.

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

Objective: Charcot-Marie-Tooth (CMT) disease 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 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050273PMC
June 2019
15 Reads

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 04 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
8 Reads
2.638 Impact Factor

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

Neurology 2019 04 27;92(17):e2027-e2037. 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
April 2019
1 Read

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

Brain 2019 05;142(5):1227-1241

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
Publisher Site
http://dx.doi.org/10.1093/brain/awz064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487329PMC
May 2019
16 Reads

POLG mutations presenting as Charcot-Marie-Tooth disease.

J Peripher Nerv Syst 2019 06 10;24(2):213-218. Epub 2019 Apr 10.

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
June 2019
2 Reads

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

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

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

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

J Biol Chem 2019 04 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
April 2019
1 Read

Histopathology of the Inner Ear in Charcot-Marie-Tooth Syndrome Caused by a Missense Variant (p.Thr65Ala) in the MPZ Gene.

Audiol Neurootol 2018 24;23(6):326-334. Epub 2019 Jan 24.

Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.

Charcot-Marie-Tooth (CMT) syndrome is a clinically and genetically heterogeneous group of neuropathies affecting both peripheral motor and sensory nerves. Progressive sensorineural hearing loss, vestibular abnormalities, and dysfunction of other cranial nerves have been described. This is the second case report of otopathology in a patient with CMT syndrome. Read More

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https://www.karger.com/Article/FullText/495176
Publisher Site
http://dx.doi.org/10.1159/000495176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421093PMC
September 2019
36 Reads

Mutational screening of the SH3TC2 gene in Greek patients with suspected demyelinating recessive Charcot-Marie-Tooth disease reveals a varied and unusual phenotypic spectrum.

J Peripher Nerv Syst 2019 03 6;24(1):125-130. Epub 2019 Feb 6.

Neurogenetics Unit, 1st Department of Neurology, Eginition Hospital, Medical School National and Kapodistrian University of Athens, Athens, Greece.

Charcot-Marie-Tooth disease type 4 C (CMT4C) is an autosomal recessive form of demyelinating peripheral neuropathy caused by mutations in SH3TC2, characterized by early onset, spine deformities, and cranial nerve involvement. We screened SH3TC2 in 50 unrelated Greek patients with suspected demyelinating Charcot-Marie-Tooth disease and pedigree compatible with recessive inheritance. All patients had been previously screened for PMP22, GJB1, and MPZ mutations. Read More

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http://dx.doi.org/10.1111/jns.12305DOI Listing
March 2019
7 Reads

MFN2 mutations in Charcot-Marie-Tooth disease alter mitochondria-associated ER membrane function but do not impair bioenergetics.

Hum Mol Genet 2019 06;28(11):1782-1800

Department of Biology, University of Padova 35131, Italy.

Charcot-Marie-Tooth disease (CMT) type 2A is a form of peripheral neuropathy, due almost exclusively to dominant mutations in the nuclear gene encoding the mitochondrial protein mitofusin-2 (MFN2). However, there is no understanding of the relationship of clinical phenotype to genotype. MFN2 has two functions: it promotes inter-mitochondrial fusion and mediates endoplasmic reticulum (ER)-mitochondrial tethering at mitochondria-associated ER membranes (MAM). Read More

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http://dx.doi.org/10.1093/hmg/ddz008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522073PMC
June 2019
9 Reads

Neurodegenerative Charcot-Marie-Tooth disease as a case study to decipher novel functions of aminoacyl-tRNA synthetases.

J Biol Chem 2019 04 14;294(14):5321-5339. Epub 2019 Jan 14.

From the Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California 92037

Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes that catalyze the first reaction in protein biosynthesis, namely the charging of transfer RNAs (tRNAs) with their cognate amino acids. aaRSs have been increasingly implicated in dominantly and recessively inherited human diseases. The most common aaRS-associated monogenic disorder is the incurable neurodegenerative disease Charcot-Marie-Tooth neuropathy (CMT), caused by dominant mono-allelic mutations in aaRSs. Read More

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http://www.jbc.org/lookup/doi/10.1074/jbc.REV118.002955
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http://dx.doi.org/10.1074/jbc.REV118.002955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462521PMC
April 2019
43 Reads

Neuregulin 1 type III improves peripheral nerve myelination in a mouse model of congenital hypomyelinating neuropathy.

Hum Mol Genet 2019 04;28(8):1260-1273

Hunter James Kelly Research Institute, University at Buffalo, Buffalo, NY, USA.

Myelin sheath thickness is precisely regulated and essential for rapid propagation of action potentials along myelinated axons. In the peripheral nervous system, extrinsic signals from the axonal protein neuregulin 1 (NRG1) type III regulate Schwann cell fate and myelination. Here we ask if modulating NRG1 type III levels in neurons would restore myelination in a model of congenital hypomyelinating neuropathy (CHN). Read More

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http://dx.doi.org/10.1093/hmg/ddy420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452193PMC
April 2019
9 Reads

Role of Alpha-methylacyl-CoA racemase gene in pathogenecity of CMT patients.

J Pak Med Assoc 2018 Jul;68(7):1039-1042

Department of Biosciences, COMSATS Institute of Information Technology Sahiwal Campus.

Objective: To find the causative mutation by linkage analysisof Charcot-Marie-Tooth disease while focussing on AMACR gene.

Methods: The case-control study was conducted from November 2016 to March 2017 in Kongju National University Korea.A family of 15 members with composite symptoms of peripheral neuropathy were enrolled. Read More

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July 2018
32 Reads
0.403 Impact Factor

A nonsense mutation in myelin protein zero causes congenital hypomyelination neuropathy through altered P0 membrane targeting and gain of abnormal function.

Hum Mol Genet 2019 01;28(1):124-132

IRCCS San Raffaele Scientific Institute, DIBIT, Milan, Italy.

Protein zero (P0) is the major structural protein in peripheral myelin, and mutations in the Myelin Protein Zero (Mpz) gene produce wide-ranging hereditary neuropathy phenotypes. To gain insight in the mechanisms underlying a particularly severe form, congenital hypomyelination (CH), we targeted mouse Mpz to encode P0Q215X, a nonsense mutation associated with the disease, that we show escapes nonsense mediated decay and is expressed in CH patient nerves. The knock-in mice express low levels of the resulting truncated protein, producing a milder phenotype when compared to patients, allowing to dissect the subtle pathogenic mechanisms occurring in otherwise very compromised peripheral myelin. Read More

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http://dx.doi.org/10.1093/hmg/ddy336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298235PMC
January 2019
10 Reads

Nerve ultrasound findings differentiate Charcot-Marie-Tooth disease (CMT) 1A from other demyelinating CMTs.

Clin Neurophysiol 2018 11 1;129(11):2259-2267. Epub 2018 Sep 1.

Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy; Neurology Division, Department of Neuroscience AOUI Verona, Verona, Italy. Electronic address:

Objective: Ulnar/median motor nerve conduction velocity (MNCV) is ≤38 m/s in demyelinating Charcot-Marie-Tooth disease (CMT). Previous nerve high resolution ultrasound (HRUS) studies explored demyelinating CMT assuming it as a homogeneous genetic/pathological entity or focused on CMT1A.

Methods: To explore the spectrum of nerve HRUS findings in demyelinating CMTs, we recruited patients with CMT1A (N = 44), CMT1B (N = 9), CMTX (N = 8) and CMT4C (N = 4). Read More

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http://dx.doi.org/10.1016/j.clinph.2018.08.016DOI Listing
November 2018
10 Reads
3.097 Impact Factor

Lessons From Leprosy: Peripheral Neuropathies and Deformities in Chronic Demyelinating Diseases.

J Hand Surg Am 2019 May 1;44(5):411-415. Epub 2018 Sep 1.

Peripheral Nerve Research Lab, Gillespie Neuroscience Research Facility, Irvine, Orange, CA; Department of Orthopaedic Surgery, University of California, Irvine, Orange, CA. Electronic address:

In light of the World Health Organization's push to accelerate progress toward a leprosy-free world by 2020, it is fitting to look back on the evolution of progress in treating lepromatous neuropathy and limb deformities. To date, no surgeon has had as great an impact on the understanding and treatment of this disease as Dr Paul Brand. Before Dr Brand's accomplishments, few surgeons participated in the management of the deformed leprous patient. Read More

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http://dx.doi.org/10.1016/j.jhsa.2018.07.007DOI Listing
May 2019
48 Reads

Genetic screening of the genes interacting with Drosophila FIG4 identified a novel link between CMT-causing gene and long noncoding RNAs.

Exp Neurol 2018 12 28;310:1-13. Epub 2018 Aug 28.

Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan; The Center for Advanced Insect Research, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan. Electronic address:

Neuron-specific knockdown of the dFIG4 gene, a Drosophila homologue of human FIG4 and one of the causative genes for Charcot-Marie-Tooth disease (CMT), reduces the locomotive abilities of adult flies, as well as causing defects at neuromuscular junctions, such as reduced synaptic branch length in presynaptic terminals of the motor neurons in third instar larvae. Eye imaginal disc-specific knockdown of dFIG4 induces abnormal morphology of the adult compound eye, the rough eye phenotype. In this study, we carried out modifier screening of the dFIG4 knockdown-induced rough eye phenotype using a set of chromosomal deficiency lines on the second chromosome. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00144886183037
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http://dx.doi.org/10.1016/j.expneurol.2018.08.009DOI Listing
December 2018
49 Reads

Targeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy.

Nat Commun 2018 08 2;9(1):3025. Epub 2018 Aug 2.

Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Göttingen, 37075, Germany.

In patients with Charcot-Marie-Tooth disease 1A (CMT1A), peripheral nerves display aberrant myelination during postnatal development, followed by slowly progressive demyelination and axonal loss during adult life. Here, we show that myelinating Schwann cells in a rat model of CMT1A exhibit a developmental defect that includes reduced transcription of genes required for myelin lipid biosynthesis. Consequently, lipid incorporation into myelin is reduced, leading to an overall distorted stoichiometry of myelin proteins and lipids with ultrastructural changes of the myelin sheath. Read More

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http://www.nature.com/articles/s41467-018-05420-0
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http://dx.doi.org/10.1038/s41467-018-05420-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072747PMC
August 2018
69 Reads
10.742 Impact Factor

What's the Function of Connexin 32 in the Peripheral Nervous System?

Authors:
Mario Bortolozzi

Front Mol Neurosci 2018 10;11:227. Epub 2018 Jul 10.

Department of Physics and Astronomy G. Galilei, University of Padua, Padua, Italy.

Connexin 32 (Cx32) is a fundamental protein in the peripheral nervous system (PNS) as its mutations cause the X-linked form of Charcot-Marie-Tooth disease (CMT1X), the second most common form of hereditary motor and sensory neuropathy and a demyelinating disease for which there is no effective therapy. Since mutations of the gene encoding Cx32 were first reported in 1993, over 450 different mutations associated with CMT1X including missense, frameshift, deletion and non-sense ones have been identified. Despite the availability of a sizable number of studies focusing on normal and mutated Cx32 channel properties, the crucial role played by Cx32 in the PNS has not yet been elucidated, as well as the molecular pathogenesis of CMT1X. Read More

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http://dx.doi.org/10.3389/fnmol.2018.00227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048289PMC
July 2018
13 Reads

The polynucleotide kinase 3'-phosphatase gene (PNKP) is involved in Charcot-Marie-Tooth disease (CMT2B2) previously related to MED25.

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

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http://dx.doi.org/10.1007/s10048-018-0555-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280876PMC
December 2018
34 Reads

Drosophila Charcot-Marie-Tooth Disease Models.

Adv Exp Med Biol 2018;1076:97-117

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

Charcot-Marie-Tooth disease (CMT) was initially described in 1886. It is characterized by defects in the peripheral nervous system, including sensory and motor neurons. Although more than 80 CMT-causing genes have been identified to date, an effective therapy has not yet been developed for this disease. Read More

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http://dx.doi.org/10.1007/978-981-13-0529-0_7DOI Listing
November 2018
5 Reads

Structure and dynamics of a human myelin protein P2 portal region mutant indicate opening of the β barrel in fatty acid binding proteins.

BMC Struct Biol 2018 06 25;18(1). Epub 2018 Jun 25.

Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.

Background: Myelin is a multilayered proteolipid sheath wrapped around selected axons in the nervous system. Its constituent proteins play major roles in forming of the highly regular membrane structure. P2 is a myelin-specific protein of the fatty acid binding protein (FABP) superfamily, which is able to stack lipid bilayers together, and it is a target for mutations in the human inherited neuropathy Charcot-Marie-Tooth disease. Read More

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http://dx.doi.org/10.1186/s12900-018-0087-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020228PMC
June 2018
15 Reads

Cochlear Implantation in Charcot-Marie-Tooth Disease: Case Report and Review of the Literature.

Case Rep Med 2018 26;2018:1760978. Epub 2018 Mar 26.

Department of Otorhinolaryngology, Mayo Clinic, Rochester, MN, USA.

Introduction: Charcot-Marie-Tooth (CMT) disease is a peripheral hereditary neuropathy associated with motor and sensory impairment and can result in profound sensorineural hearing loss (SNHL). Currently, the role of cochlear implantation in the setting of CMT and other progressive peripheral neurodegenerative disorders is not well established.

Methods: Case report and review of the English literature. Read More

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http://dx.doi.org/10.1155/2018/1760978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892247PMC
March 2018
9 Reads