• Journal of Genetic Medicine
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• 제18권2호
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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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• 제7권2호
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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.

• 대한임상검사과학회지
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• 제53권2호
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• pp.151-157
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• 2021

선천성 유전질환인 CMT와 후천성 면역 매개 질환인 CIDP는 임상적 증상이 유사하므로 두 질환의 감별진단을 위해서는 말초신경의 전기생리학적 특징을 비교하는 것이 도움이 될 수 있다. 본 연구는 CIDP와 CMT 1형으로 확진된 환자의 신경전도검사 결과 중 감각신경전도검사의 주요 지표별 결과를 후향적으로 정량분석하여 두 질환군의 전기생리학적 특징을 규명하고자 하였다. CIDP (N=35)와 CMT1 (N=30)로 확진된 환자의 dCNAP와 SNCV를 이용하여 두 질환군의 중증도 분석, 유의성 검정, 비정상 범위별 비율분석 및 상관분석을 실시하여 통계적 차이를 기반으로 특징을 비교하였다. 두 질환 모두 전신성 말초신경다발신경병증의 특징이 관찰되었고, 장딴지신경의 손상이 가장 심한 것으로 확인되었다. CMT1군은 탈수초성 및 축삭성 신경병증을 동반하는 전신성 신경병증이고, CIDP보다 더 중증의 신경병증임이 확인되었다. 또한, 상관계수 및 산점도 분석에서 CMT1은 신경 손상 범위가 전체 신경에서 균등한 전기생리학적 특징이 관찰되었다. 감각신경전도검사의 결과를 기반으로한 본 연구결과가 CIDP와 CMT 1형의 감별진단 및 연구에 도움이 될 것으로 사료된다.

• 동의신경정신과학회지
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• 제17권1호
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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.

• Molecules and Cells
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• 제23권1호
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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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• 제40권4호
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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.

• 생명과학회지
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• 제29권7호
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• pp.800-808
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• 2019

샤르코-마리-투스병(Charcot-Marie-Tooth disease: CMT)은 희귀 말초신경병의 그룹으로, 진행성 근육 약화 및 위축, 감각 소실, 상지 및 하지의 무반사 증상을 나타낸다. CMT1A는 PMP22 유전자가 존재하는 17p12 지역의 직렬 중복으로 발병하는데, 유전자형-표현형의 상관성이 느슨하여 2차 유전적 요인의 존재를 암시한다. 최근 MIR149의 rs71428439 (n.83A>G)와 rs2292832 (n.86T>C) 변이가 후기 발병 및 가벼운 증상의 표현형과 연관성이 있는 것으로 보고되었다. 본 연구는 CMT1A 기계내 임상적 표현형의 이질성이 MIR149의 SNP과 연관성이 있는지를 규명하기 위해 수행하였으며, 조사 대상으로는 가계내 표현형의 차이가 심한 6 CMT1A 대 가계를 대상으로 하였다. 그 결과, MIR149의 rs71428439와 s2292832 유전자형은 가족내의 늦은 발병과 약한 중증도의 유전적 요인으로 작용할 수 있음을 제시하였다. 특히, AG+GG (n.83A>G)와 TC+CC 유전자형(n.86T>C)은 발병 시기가 늦고 경미한 증상을 보였다. 운동신경 전기전도도(MNCV)는 MIR149 유전형과 연관이 없는 것으로 보였는데, 이러한 결과는 이전 연구와 일치한다. 따라서 본 연구는 MIR149의 rs71428439와 rs2292832 변이는 CMT1A 가계내 표현형적 이질성의 원인 중 하나로 작용할 가능성을 제시한다. 본 연구는 가계 내 증상의 차이가 심한 6 대가족을 사용하여 연구를 수행한 것은 의미가 크다고 여겨지며, 이런 결과는 CMT1A 환자의 분자 진단과 치료에 도움을 줄 수 있을 것으로 기대된다.

• Journal of Genetic Medicine
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• 제19권1호
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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.

• 척추신경추나의학회지
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• 제2권1호
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• pp.99-114
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• 2007

Objectives : The purpose of this study was to introduce the Chuna Manual Therapy (CMT) using Bong (a type of stick which is called 'bong') as a part of Oriental Medicine. Methods : We searched several traditional methods of CMT using Bong, either individual contact to specialist of CMT using Bong or referred to publications, and summarized briefly for introduction. Authors also made a comparative study between existing CMT and CMT using the bong. Results & Conclusions : The indications of Bong CMT are regarded as acute or chronic pain syndrome, whiplash associated disorders, facet syndrome, vertebral misalignment, chronic fatigue syndrome, obesity and also lower extremity length difference caused by malalignment of vertebrae and pelvic bone. The Meridian Muscle Therapy by pressing down using the Bong can be carried out on the imbalances of the muscle by shortening and lengthening contraction. CMT with Bong is considered more effective than other existing CMT in terms of effectiveness. In the case of pelvic correction which needs a tremendous amount of force, it can reduce the force required effectively. This fact can be inferred by the theory of composition and decomposition of force during the transmission of power. We can perform Bong CMT feeling less fatigued subsequently than general CMT. Pressing down with flexed fingers to grip bong acts on the contraction of flexor digiti and extensor digiti muscle, this protects the $doctor^{\circ}{\emptyset}s$ wrist joints from injury. The bong which acts as a tool between the doctor and the patient, while being given treatment, absorbs and spreads out the direct impact from the patient to the doctor. CMT with Bong is able to apply to both existing massage therapies with the hand. The bong appliance can be used in all applications, particularly, but not limited to; Orthopedic and Manual Correction Therapy, Meridian Muscle Pressing, Exercise Therapy, and Meridian Point Manual Pressing Therapy. CMT with Bong belongs to the category of oriental rehabilitation and Chuna manual medicine.

• 동의신경정신과학회지
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• 제17권1호
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• pp.37-57
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• 2006

Objective : This research investigates the effect of the CMT and MCMT on Alzheimer‘s disease. Methods : The effects of the CMT and MCMT extract 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, GFAP, CD68 abd CD11b; (5) the infarction area of the hippocampus in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. Results : 1. The CMT and MCMT extract suppressed the expression of APP, AChE, and mRNA in PC-12 cells treated with CT-105. 2. The CMT and MCMT extract suppressed the AChE activity, and the production of APP significantly in PC-12 cells treated with CT-105. 3. For the CMT and MCMT extract 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 MCMT extract suppressed the over-expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, GFAP, CD68 abd CD11bCD68/GFAP, in the mice with Alzheimer's disease induced by ${\beta}A$. 5. The CMT and MCMT extract reduced the infarction area of hippocampus with Alzheimer's disease induced by ${\beta}A$ 6. The MCMT showed more excellent effects than CMT in the every experiments except PC-12 cells. Conclusions : These results suggest that the CMT and MCMT extract may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the CMT and MCMT extract for Alzheimer's disease is suggested for future research.