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

Abstract

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.

Case report: A novel homozygous histidine triad nucleotide-binding protein 1 mutation featuring distal hereditary motor-predominant neuropathy with rimmed vacuoles

“…Distal hereditary motor neuropathy (dHMN) is a less common variant of CMT characterized by motor-predominant axonal involvement with absent or minimal sensory deficits ( 5 , 6 ). Mutations in more than 100 genes have been associated with CMT ( 7 ). CMT disease can be sub-classified according to median motor conduction velocity into demyelinating (< 35 m/s), intermediate (35–45 m/s), and axonal (>45 m/s) forms.…”