• Journal of Genetic Medicine
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• v.18 no.2
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• pp.83-93
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• 2021

Charcot-Marie-Tooth disease (CMT) is the most common hereditary motor and sensory peripheral neuropathy. CMT is usually classified into two categories based on pathology: demyelinating CMT type 1 (CMT1) and axonal CMT type 2 (CMT2) neuropathy. CMT1 can be distinguished by assessing the median motor nerve conduction velocity as greater than 38 m/s. The main clinical features of axonal CMT2 neuropathy are distal muscle weakness and loss of sensory and areflexia. In addition, they showed unusual clinical features, including delayed development, hearing loss, pyramidal signs, vocal cord paralysis, optic atrophy, and abnormal pupillary reactions. Recently, customized treatments for genetic diseases have been developed, and pregnancy diagnosis can enable the birth of a normal child when the causative gene mutation is found in CMT2. Therefore, accurate diagnosis based on genotype/phenotypic correlations is becoming more important. In this review, we describe the latest findings on the phenotypic characteristics of axonal CMT2 neuropathy. We hope that this review will be useful for clinicians in regard to the diagnosis and treatment of CMT.

• Annals of Clinical Neurophysiology
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• v.7 no.2
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• pp.65-74
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• 2005

Charcot-Marie-Tooth (CMT) disease was described by Charcot and Marie in France and, independently, by Tooth in England in 1886. CMT is the most common form of inherited motor and sensory neuropathy, and is a genetically heterogeneous disorder of the peripheral nervous system. Therefore, many genes have been identified as CMT-causative genes. Traditionally, subclassification of CMT have been divided into autosomal dominant inherited demyelinating (CMT1) and axonal (CMT2) neuropathies, X-linked neuropathy (CMTX), and autosomal recessive inherited neuropathy (CMT4). Recently, intermediate type (CMT-Int) with NCVs between CMT1 and CMT2 is considered as a CMT type. There are several related peripheral neuropathies, such as $D{\acute{e}}j{\acute{e}}rine$-Sottas neuropathy (DSN), congenital hypomyelination (CH), hereditary neuropathy with liability to pressure palsies (HNPP) and giant axonal neuropathy (GAN). Great advances have been made in understanding the molecular basis of CMT, and 17 distinct genetic causes of CMT have been identified. The number of newly discovered mutations and identified genetic loci is rapidly increasing, and this expanding list has proved challenging for physicians trying to keep up with the field. Identifying the genetic cause of inherited neuropathies is often important to determine at risk family members as well as diagnose the patient. In addition, the encouraging studies have been published on rational potential therapies for the CMT1A. Now, we develop a model of how the various genes may interact in the pathogenesis of CMT disorder.

• Korean Journal of Clinical Laboratory Science
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• v.53 no.2
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• pp.151-157
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• 2021

Charcot-Marie-Tooth disease (CMT) is a slowly progressive hereditary degenerative disease and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired immune-mediated disorder characterized by weakness and sensory deficits. The purpose of this study was to analyze and compare the electrophysiological characteristics observed in sensory nerve conduction studies (SNCS) of both diseases. A retrospective study of 65 patients with a diagnosis of CIDP (N=35) and CMT type I (N=30) was performed. This study analyzed No potentials ratio, distal compound nerve action potential (dCNAP) of various nerve types, and a correlation coefficient analysis of the sensory nerve conduction velocity (SNCV). As a result, I found that CMT 1 was more severe systemic demyelinating and axonal polyneuropathy better than CIDP (P<0.05). In a quantitative analysis of dCNAP and SNCV, especially sural nerve was the most severe nerve injury observed in both diseases. In correlation and scatter plot analysis, CMT 1 showed relatively high correlations compared to CIDP based on the correlation coefficient analysis (Fisher's Z test) of SNCV. The results of this study suggested that CMT 1 showed the slowness in SNCV, one of the characteristics of demyelinating polyneuropathy, and this slowing had a uniform pattern. In conclusion, electrophysiological characteristic of SNCS may be useful in the diagnosis and research between patients with CMT 1 and CIDP.

• Journal of Oriental Neuropsychiatry
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• v.17 no.1
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• pp.59-78
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• 2006

Objective : This research investigates the effect of the CMT and SCMT on Alzheimer's disease. Methods : The effects of the CMT and SCMT on (1) amyloid precursor proteins(APP), acetylcholinesterase(AChE) mRNA of PC-12 cells treated with CT-105; (2) the AChE activity and the APP production of PC-12 cell treated with CT-105; (3) the behavior; (4) expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA; (5) the infarction area of the hippocampus in Alzheimer's disease mice induced with CT105 & ${\beta}A$ were investigated Rresults : 1. The CMT and SCMT suppressed the expression of APP, AChE mRNA in PC-12 cells treated with CT-105 2. The CMT and SCMT suppressed the AChE activity, and the production of APP significantly in PC-12 cells treated with CT-105. 3. For the CMT and SCMT group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}A$ in the Morris water maze experiment, which measured stop-through latency, and distance movement-through latency 4. The CMT and SCMT suppressed the over-expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA in the mice with Alzheimer's disease induced by ${\beta}A$. 5. The CMT and SCMT reduced the infarction area of hippocampus with Alzheimer's disease induced by ${\beta}A$. Conclusions : These results suggest that the CMT and SCMT may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the CMT and SCMT for Alzheimer's disease is suggested for future research.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.471-476
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• 2006

Chongmyung-tang(CMT, 聰明湯), oriental herbal medicine which consists of Polygaglae Radix(遠志), Acori Graminei Rhizoma(石菖蒲) and Hoelen(白茯神) has effect on amnesia, dementia. In order to evaluate effect of CMT on memory and learning in mice, CMT extract was used for studies. This paper describes the effects of CMT extract on memory and learning processes by using the passive and active avoidance performance tests, novel object recognition task and water maze task. The CMT extract ameliorated the memory retrieval deficit induced by ethanol in the passive avoidance responses but did not affect ambulatory activity of normal mice. These results suggest that CMT has an ameliorating effect on memory retrieval impairment. CMT extract decreased spontaneous motor activity(SMA) in the latter sessions of memory registration in active avoidance responses. These results suggest that CMT has partly transquilizing or antianxiety effects. In novel object recognition task to measure visual recognition memory, CMT-administered mice enhanced in long term memory for 1-3 days. In water maze task to measure spatial learning, which requires the activation of NMDA receptors in the hippocampus, spatial learning in CMT-administered mice was faster than in wild-type mice. These results suggest that CMT enhances memory and activates NMDA receptors.

• Molecules and Cells
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• v.23 no.1
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• pp.39-48
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• 2007

Charcot-Marie-Tooth (CMT) disease and hereditary neuropathy with liability to pressure palsies (HNPP) are frequent forms of genetically heterogeneous peripheral neuropathies. Reciprocal unequal crossover between flanking CMT1A-REPs on chromosome 17p11.2-p12 is a major cause of CMT type 1A (CMT1A) and HNPP. The importance of a sensitive and rapid method for identifying the CMT1A duplication and HNPP deletion is being emphasized. In the present study, we established a molecular diagnostic method for the CMT1A duplication and HNPP deletion based on hexaplex PCR of 6 microsatellite markers (D17S921, D17S9B, D17S9A, D17S918, D17S4A and D17S2230). The method is highly time-, cost- and sample-saving because the six markers are amplified by a single PCR reaction and resolved with a single capillary in 3 h. Several statistical and forensic estimates indicated that most of these markers are likely to be useful for diagnosing the peripheral neuropathies. Reproducibility, as determined by concordance between independent tests, was estimated to be 100%. The likelihood that genotypes of all six markers are homozygous in randomly selected individuals was calculated to be $1.6{\times}10^{-4}$, which indicates that the statistical error rate for this diagnosis of HNPP deletion is only 0.016%.

• Clinical and Experimental Reproductive Medicine
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• v.40 no.4
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• pp.163-168
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• 2013

Objective: Preimplantation genetic diagnosis (PGD) is an assisted reproductive technique for couples carrying genetic risks. Charcot-Marie-Tooth (CMT) disease is the most common hereditary neuropathy, with a prevalence rate of 1/2,500. In this study, we report on our experience with PGD cycles performed for CMT types 1A and 2F. Methods: Before clinical PGD, we assessed the amplification rate and allele drop-out (ADO) rate of multiplex fluorescent polymerase chain reaction (PCR) followed by fragment analysis or sequencing using single lymphocytes. We performed six cycles of PGD for CMT1A and one cycle for CMT2F. Results: Two duplex and two triplex protocols were developed according to the available markers for each CMT1A couple. Depending on the PCR protocols, the amplification rates and ADO rates ranged from 90.0% to 98.3% and 0.0% to 11.1%, respectively. For CMT2F, the amplification rates and ADO rates were 93.3% and 4.8%, respectively. In case of CMT1A, 60 out of 63 embryos (95.2%) were diagnosed and 13 out of 21 unaffected embryos were transferred in five cycles. Two pregnancies were achieved and three babies were delivered without any complications. In the case of CMT2F, a total of eight embryos were analyzed and diagnosed. Seven embryos were diagnosed as unaffected and four embryos were transferred, resulting in a twin pregnancy. Two healthy babies were delivered. Conclusion: This is the first report of successful pregnancy and delivery after specific PGD for CMT disease in Korea. Our PGD procedure could provide healthy babies to couples with a high risk of transmitting genetic diseases.

• Journal of Life Science
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• v.29 no.7
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• pp.800-808
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• 2019

Charcot-Marie-Tooth disease (CMT) is a group of rare peripheral neuropathies characterized by progressive muscle weakness and atrophy and areflexia in the upper and lower extremities. The most common subtype of CMT is CMT1A, which is caused by a tandem duplication of the PMP22 gene in the 17p12 region. Patients with CMT1A show a loose genotype-phenotype correlation, which suggests the existence of secondary genetic or association factors. Recently, polymorphisms of rs71428439 (n.83A>G) and rs2292832 (n.86T>C) in the MIR149 have been reported to be associated with late onset and mild phenotypic CMT1A severity. The aim of this study was to examine the intrafamilial heterogeneities of clinical phenotypes according to the genotypes of these two SNPs in MIR149. For this study, we selected 6 large CMT1A families who showed a wide range of phenotypic variation. This study suggested that both SNPs were related to the onset age and severity in the dominant model. In particular, the AG+GG (n.83A>G) and TC+CC genotypes (n.86T>C) were associated to late onset and mild symptoms. Motor nerve conduction velocity (MNCV) was not related to the MIR149 genotypes. These results were consistent with the previous studies. Therefore, we suggest that the rs71428439 and rs2292832 variants in MIR149 may serve as genetic modifiers of CMT1A intrafamilial phenotypic heterogeneity, as they have a role in the unrelated patients. This is the first study to show an association using large families with variable clinical CMT1A phenotypes. The results will be helpful in the molecular diagnosis and treatment of patients with CMT1A.

• Journal of Society of Preventive Korean Medicine
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• v.23 no.2
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• pp.1-10
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• 2019

Backgrounds : In 2017, National Health Insurance implemented the pilot coverage program for Chuna manual therapy(CMT). 65 Korean Medicine(KM) hospitals and clinics were selected in the program to monitor the effectiveness and patients' satisfaction of insured CMT. Objectives : This study aimed to evaluate patients' satisfaction of CMT in the pilot coverage program of National Health Insurance. Methods : Survey participants were recruited among the patients who used CMT at the designated organizations. On-line questionnaire link was sent to the smart phones of patients who agreed to participate in the survey and provide personal contact information. The questionnaire consisted of the basic charactersitics of respondents, imformation on using CMT satisfaction with CMT and willingness to recommend CMT to others. The answers that were automatically coded and saved were statistically analyzed. Results : Of 386 participants who completed the questionnaire, 92.8% satisfied or strongly satisfied with the CMT. Most frequent reason of satisfaction was 'Good effectiveness', and there was no difference in satisfaction between patients of hospital and those of clinics. Patients with the highest and the lowest level of pain satisfied more than those with other pain levels(p=0.003), but the level of copayment and reasons of CMT use did not affect the satisfaction results(p=0.405). The proportions of respondents who had willingness to recommend CMT to others and to revisit for CMT use were 97.8% and 98.8%, respectively. Conclusions : Most patients were satisfied with CMT in the pilot coverage program, and it can provide the rationale for expanding the insurance coverage of CMT to all KM hospitals and clinics.

• Journal of Genetic Medicine
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• v.19 no.1
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• pp.7-13
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• 2022

Purpose: Preimplantation genetic testing for monogenic disorders (PGT-M) has been successfully used to prevent couples with monogenic disorders from passing them on to their child. Charcot-Marie-Tooth Disease (CMT) is a genetic disorder characterized by progressive extremity muscle degeneration and loss of sensory function. For the first time in Korea, we report our experience of applying single nucleotide polymorphism genotyping and karyomapping for PGT-M of CMT disease. Materials and Methods: Prior to clinical PGT-M, preclinical tests were performed using genotypes of affected families to identify informative single-nucleotide polymorphisms associated with mutant alleles. We performed five cycles of in vitro fertilization PGT-M in four couples with CMT1A, CMT2A, and CMT2S in CHA Fertility Center, Seoul Station. Results: From July 2020 through August 2021, five cycles of PGT-M with karyomapping in four cases with CMT1 and CMT2 were analyzed retrospectively. A total of 17 blastocysts were biopsied and 15 embryos were successfully diagnosed (88.2%). Ten out of 15 embryos were diagnosed as unaffected (66.7%). Five cycles of PGT-M resulted in four transfer cycles, in which four embryos were transferred. Three clinical pregnancies were achieved (75%) and the prenatal diagnosis by amniocentesis for all three women confirmed PGT-M of karyomapping. One woman delivered a healthy baby uneventfully and two pregnancies are currently ongoing. Conclusion: This is the first report in Korea on the application of karyomapping in PGT-M for CMT patients. This study shows that karyomapping is an efficient, reliable and accurate diagnostic method for PGT-M in various types of CMT diseases.