J Korean Neurol Assoc.  2024 May;42(2):126-137. 10.17340/jkna.2023.0076.

Comparative Analysis on Methylation Levels of Nerve and Stress Related Genes in Charcot-Marie-Tooth Disease Type 1A Patients

• Nam DE
• Hwang SH
• Yim JY
• Choi BO
• Chung KW

• KMID: 2554816
• DOI: http://doi.org/10.17340/jkna.2023.0076

Abstract

Background
Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by duplication of the 17p12 region including PMP22 gene. In CMT1A patients, anticipation showing increased severity by generations has been reported in the CMT1A patients. It has also been reported that severity increases in the non-de novo cases than in the de novo cases. This study was performed to examine epigenetic differences between CMT1A cases and controls as well as between de novo cases and non-de novo cases.
Methods
This study examined 40 Korean CMT1A patients and 11 controls. Methylation level was determined using the SureSelect XT Methyl-Seq reagent kit and bisulfite sequence mapping program.
Results
Many differentially methylated CpG sites (DMCs) were identified in the comparison between cases and controls and between de novo cases and non-de novo cases. Most DMCs were located within or nearby genes related to the nervous system, mental stress, and motor ability.
Conclusions
This study is the first epigenetic study to uncover the mechanism of clinical heterogeneity among CMT1A patients. We suggest that weak severity in the de novo cases than the non-de novo cases may be related to the epigenomic differences in the nerve and stress-related genes.

Keyword

Charcot-Marie-Tooth disease; DNA methylation; CpG islands; De novo mutation