scholarly journals Held Up in Traffic—Defects in the Trafficking Machinery in Charcot-Marie-Tooth Disease

2021 ◽  
Vol 14 ◽  
Author(s):  
Ronja Markworth ◽  
Mathias Bähr ◽  
Katja Burk
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Intracellular Transport ◽  
Early Adulthood ◽  
Sensory Neuropathy ◽  
Common Denominator ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Trafficking Defects ◽  
Tooth Disease

Charcot-Marie-Tooth disease (CMT), also known as motor and sensory neuropathy, describes a clinically and genetically heterogenous group of disorders affecting the peripheral nervous system. CMT typically arises in early adulthood and is manifested by progressive loss of motor and sensory functions; however, the mechanisms leading to the pathogenesis are not fully understood. In this review, we discuss disrupted intracellular transport as a common denominator in the pathogenesis of different CMT subtypes. Intracellular transport via the endosomal system is essential for the delivery of lipids, proteins, and organelles bidirectionally to synapses and the soma. As neurons of the peripheral nervous system are amongst the longest neurons in the human body, they are particularly susceptible to damage of the intracellular transport system, leading to a loss in axonal integrity and neuronal death. Interestingly, defects in intracellular transport, both in neurons and Schwann cells, have been found to provoke disease. This review explains the mechanisms of trafficking and subsequently summarizes and discusses the latest findings on how defects in trafficking lead to CMT. A deeper understanding of intracellular trafficking defects in CMT will expand our understanding of CMT pathogenesis and will provide novel approaches for therapeutic treatments.

scholarly journals Identification of Candidate Genes Associated with Charcot-Marie-Tooth Disease by Network and Pathway Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Min Zhong ◽  
Qing Luo ◽  
Ting Ye ◽  
XiDan Zhu ◽  
Xiu Chen ◽  
...  
Keyword(s):  
Nervous System ◽  
Candidate Genes ◽  
Peripheral Nervous System ◽  
Molecular Mechanisms ◽  
Clinical Genetic ◽  
Systematic Analysis ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Functional Features ◽  
Tooth Disease

Charcot-Marie-Tooth Disease (CMT) is the most common clinical genetic disease of the peripheral nervous system. Although many studies have focused on elucidating the pathogenesis of CMT, few focuses on achieving a systematic analysis of biology to decode the underlying pathological molecular mechanisms and the mechanism of its disease remains to be elucidated. So our study may provide further useful insights into the molecular mechanisms of CMT based on a systematic bioinformatics analysis. In the current study, by reviewing the literatures deposited in PUBMED, we identified 100 genes genetically related to CMT. Then, the functional features of the CMT-related genes were examined by R software and KOBAS, and the selected biological process crosstalk was visualized with the software Cytoscape. Moreover, CMT specific molecular network analysis was conducted by the Molecular Complex Detection (MCODE) Algorithm. The biological function enrichment analysis suggested that myelin sheath, axon, peripheral nervous system, mitochondrial function, various metabolic processes, and autophagy played important roles in CMT development. Aminoacyl-tRNA biosynthesis, metabolic pathways, and vasopressin-regulated water reabsorption were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway network, suggesting that these pathways may play key roles in CMT occurrence and development. According to the crosstalk, the biological processes could be roughly divided into a correlative module and two separate modules. MCODE clusters showed that in top 3 clusters, 13 of CMT-related genes were included in the network and 30 candidate genes were discovered which might be potentially related to CMT. The study may help to update the new understanding of the pathogenesis of CMT and expand the potential genes of CMT for further exploration.

scholarly journals Relapsing Remitting Multiple Sclerosis in X-Linked Charcot-Marie-Tooth Disease with Central Nervous System Involvement

2015 ◽  
Vol 2015 ◽  
pp. 1-3 ◽  
Author(s):  
Georgios Koutsis ◽  
Georgia Karadima ◽  
Paraskewi Floroskoufi ◽  
Maria Raftopoulou ◽  
Marios Panas
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Brain Mri ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Tooth Disease

We report a patient with relapsing remitting multiple sclerosis (MS) and X-linked Charcot-Marie-Tooth disease (CMTX), carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr) which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars). Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.

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

2020 ◽  
Vol 41 (7) ◽  
pp. 870-880 ◽  
Author(s):  
Glenn B. Pfeffer ◽  
Tyler Gonzalez ◽  
James Brodsky ◽  
John Campbell ◽  
Chris Coetzee ◽  
...  
Keyword(s):  
Consensus Statement ◽  
Sensory Neuropathy ◽  
Comprehensive Approach ◽  
Foot And Ankle ◽  
Clinical Experiences ◽  
Consensus Guidelines ◽  
Level Of Evidence ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

Background: Charcot-Marie-Tooth (CMT) disease is a hereditary motor-sensory neuropathy that is often associated with a cavovarus foot deformity. Limited evidence exists for the orthopedic management of these patients. Our goal was to develop consensus guidelines based upon the clinical experiences and practices of an expert group of foot and ankle surgeons. Methods: Thirteen experienced, board-certified orthopedic foot and ankle surgeons and a neurologist specializing in CMT disease convened at a 1-day meeting. The group discussed clinical and surgical considerations based upon existing literature and individual experience. After extensive debate, conclusion statements were deemed “consensus” if 85% of the group were in agreement and “unanimous” if 100% were in support. Conclusions: The group defined consensus terminology, agreed upon standardized templates for history and physical examination, and recommended a comprehensive approach to surgery. Early in the course of the disease, an orthopedic foot and ankle surgeon should be part of the care team. This consensus statement by a team of experienced orthopedic foot and ankle surgeons provides a comprehensive approach to the management of CMT cavovarus deformity. Level of Evidence: Level V, expert opinion.

Quantitative measurement of duplicated DNA as a diagnostic test for Charcot-Marie-Tooth disease type 1a

1993 ◽  
Vol 39 (9) ◽  
pp. 1845-1849 ◽  
Author(s):  
G W Hensels ◽  
E A Janssen ◽  
J E Hoogendijk ◽  
L J Valentijn ◽  
F Baas ◽  
...  
Keyword(s):  
Preliminary Investigation ◽  
Sensory Neuropathy ◽  
Disease Type ◽  
Chromosome 17 ◽  
Hereditary Neuropathy ◽  
Chromosomal Dna ◽  
Gene Encoding ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

Abstract Charcot-Marie-Tooth disease type 1 (CMT1) is a hereditary motor and sensory neuropathy. The autosomal dominant subtype is often linked with a large duplication on chromosome 17p11.2. The gene encoding the peripheral myelin protein PMP 22 (the critical gene in this subtype of CMT1) is located within this duplication. To detect this duplication in chromosomal DNA from individuals thought to have CMT1, we compared the hybridization signals of two DNA probes within this duplication (VAW412R3a and VAW409R3a) with the signal of a reference probe (E3.9). When duplication was present, the signals from the first two probes increased from 100% (for nonduplicated samples) to 145% and 142%, respectively. The day-to-day variance was 3.7% and 5.1%, respectively. We demonstrated this DNA duplication in 49 of 95 DNA samples from unrelated individuals thought to have CMT1. Moreover, because hereditary neuropathy with liability to pressure palsies (HNPP) is based on a DNA deletion in the same area of chromosome 17, this quantitative test may be useful in establishing the presence of HNPP. In a preliminary investigation, four unrelated patients with HNPP yielded test values of 63% and 54%, respectively, of those for nonduplicated samples (CV 19% and 18%, respectively; n = 4), suggesting a deletion in 17p11.2.

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