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 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 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.

scholarly journals Neural and Molecular Features on Charcot-Marie-Tooth Disease Plasticity and Therapy

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Paula Juárez ◽  
Francesc Palau
Keyword(s):  
Schwann Cell ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Mitochondrial Dynamics ◽  
Sensory Nerves ◽  
Peripheral Neuropathies ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Molecular Features ◽  
Tooth Disease

In the peripheral nervous system disorders plasticity is related to changes on the axon and Schwann cell biology, and the synaptic formations and connections, which could be also a focus for therapeutic research. Charcot-Marie-Tooth disease (CMT) represents a large group of inherited peripheral neuropathies that involve mainly both motor and sensory nerves and induce muscular atrophy and weakness. Genetic analysis has identified several pathways and molecular mechanisms involving myelin structure and proper nerve myelination, transcriptional regulation, protein turnover, vesicle trafficking, axonal transport and mitochondrial dynamics. These pathogenic mechanisms affect the continuous signaling and dialogue between the Schwann cell and the axon, having as final result the loss of myelin and nerve maintenance; however, some late onset axonal CMT neuropathies are a consequence of Schwann cell specific changes not affecting myelin. Comprehension of molecular pathways involved in Schwann cell-axonal interactions is likely not only to increase the understanding of nerve biology but also to identify the molecular targets and cell pathways to design novel therapeutic approaches for inherited neuropathies but also for most common peripheral neuropathies. These approaches should improve the plasticity of the synaptic connections at the neuromuscular junction and regenerate cell viability based on improving myelin and axon interaction.

Central nervous system involvement in axonal Charcot-Marie-Tooth disease

2009 ◽  
Vol 41 (1) ◽  
pp. 148-150
Author(s):  
Xinli Du ◽  
G. Frederick Wooten ◽  
Julie A. Matsumoto ◽  
Lawrence H. Phillips
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Involvement ◽  
Charcot Marie Tooth ◽  
System Involvement ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

scholarly journals Charcot Marie Tooth disease type 4J with complex central nervous system features

2018 ◽  
Vol 5 (2) ◽  
pp. 222-225 ◽  
Author(s):  
James P. Orengo ◽  
Pravin Khemani ◽  
John W. Day ◽  
Jun Li ◽  
Carly E. Siskind
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Disease Type ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

scholarly journals A case of X-linked Charcot-Marie-tooth disease type 1 manifesting as recurrent alternating hemiplegia with transient cerebral white matter lesions

2021 ◽  
Vol 23 (2) ◽  
pp. 130-133
Author(s):  
Minsung Kang ◽  
Sun-Jae Hwang ◽  
Jin-Hong Shin ◽  
Dae-Seong Kim
Keyword(s):  
Nervous System ◽  
Clinical Manifestations ◽  
White Matter Lesions ◽  
Disease Type ◽  
Cerebral White Matter ◽  
Hereditary Neuropathy ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

X-linked Charcot Marie Tooth disease type 1 (CMTX1) is a clinically heterogenous X-linked hereditary neuropathy caused by mutation of the gene encoding gap junction beta 1 protein (GJB1). Typical clinical manifestations of CMTX1 are progressive weakness or sensory disturbance due to peripheral neuropathy. However, there have been some CMTX1 cases with accompanying central nervous system (CNS) manifestations. We report the case of a genetically confirmed CMTX1 patient who presented recurrent transient CNS symptoms without any symptom or sign of peripheral nervous system involvement.

scholarly journals Transient, Recurrent Central Nervous System Clinical Manifestations of X-Linked Charcot-Marie-Tooth Disease Presenting with Very Long Latency Periods between Episodes: Is Prolonged Sun Exposure a Provoking Factor?

2020 ◽  
Vol 2020 ◽  
pp. 1-5 ◽  
Author(s):  
Andria Tziakouri ◽  
Konstantinos Natsiopoulos ◽  
Kleopas A. Kleopa ◽  
Costas Michaelides
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Prolonged Exposure ◽  
Clinical Manifestations ◽  
Sun Exposure ◽  
Foot Deformities ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Long Latency ◽  
Tooth Disease

Charcot-Marie-Tooth disease is one of the most common inherited neurological disorders affecting the peripheral nervous system. The common clinical manifestations of the disease are distal muscle weakness and atrophy, often associated with a characteristic steppage gait and foot deformities. Transient acute and recurrent or chronic central nervous system manifestations, predominantly, dysarthria, dysphagia, motor weakness, and ataxia, have been recognized as a feature of the X-linked type 1 of CMT (CMTX1). The CNS symptoms occur typically in young age and often precede the clinical manifestation of the polyneuropathy. Several predisposing factors such as exercise, fever, and returning from areas of high altitude have been described as triggers of the CNS symptoms; however, in many cases, a substantial cause remains undetermined. In this report, we describe a patient with three attacks of transient CNS deficits at the ages of 11, 21, and 38 years, respectively, which were also accompanied by transient white matter abnormalities on MRI. Two of the attacks occurred after prolonged exposure to sunlight. In our knowledge, this is the first documented case with such long latency periods between CNS attacks as well as the only report describing intense sun exposure as a possible provoking factor.

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