1.Classification and molecular diagnostic procedure for Chacort-Marie-Tooth disease.
Chinese Journal of Medical Genetics 2012;29(5):553-557
Charcot-Marie-Tooth disease (CMT) is the most common form of hereditary neuropathy with significant clinical and genetic heterogeneity. So far 28 genes have been cloned. The main clinical manifestations of CMT include progressive distal muscle wasting and weakness, impaired distal sensation, and diminishing or loss of tendon reflex. Patients may be classified into demyelinating type (CMT1) and axonal type (CMT2) according to electrophysiological and pathological characteristics. Establishment of a standard diagnostic procedure based on clinical, electrophysiological and pathological findings will enable accurate diagnosis in most CMT patients and provide guidance for gene consulting and prognosis.
Charcot-Marie-Tooth Disease
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classification
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diagnosis
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genetics
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Humans
3.Genetic profile of Chinese patients with Charcot-Marie-Tooth disease.
Zhi-Yuan OUYANG ; You CHEN ; Da-Qiang QIN ; Zhi-Dong CEN ; Xiao-Sheng ZHENG ; Fei XIE ; Si CHEN ; Hao-Tian WANG ; De-Hao YANG ; Xin-Hui CHEN ; Le-Bo WANG ; Bao-Rong ZHANG ; Wei LUO
Chinese Medical Journal 2020;133(21):2633-2634
4.Studies of electromyography and genetics in children with Charcot-Marie-Tooth disease type 1.
Xiao-Li PAN ; Nan-Nan ZHANG ; Hong-Lian YE ; Yue-Fei ZHAO ; Hong GAO
Chinese Journal of Contemporary Pediatrics 2011;13(8):647-650
OBJECTIVETo study the electromyographic and genetic characteristics in children with Charcot-Marie-Tooth disease type 1 (CMT1).
METHODSRoutine electromyography and nerve conduction were performed in 24 children with CMT1. Polymerase chain reaction (PCR) combined with restriction enzyme digestion was used to detect gene duplication on chromosome 17p11.2-12. Ten healthy children served as the control group.
RESULTSThe peripheral nerve conduction velocity slowed or disappeared in all of the 24 patients (100%). The lesions of the sensory nerves were more severe than the motor nerves, and the lesions of the lower limbs were more severe than the upper limbs. Of 72 muscles detected, 40 (56%) showed neurogenic lesions. The older the patients, the more severe the muscle lesions. Specific junction fragments (1760 bp) were identified in 13 (54%) out of 24 patients, but were not identified in the healthy controls.
CONCLUSIONSThe electromyographic changes are characterized by peripheral nerve conduction velocities slowing and neurogenic lesions of muscles in children with CMT1. The PCR combined with restriction enzyme digestion may be a simple and accurate method for gene diagnosis of CMT1.
Adolescent ; Charcot-Marie-Tooth Disease ; genetics ; physiopathology ; Child ; Electromyography ; Female ; Humans ; Male ; Neural Conduction
5.Research advance of underlying pathogenesis and target therapies in Charcot-Marie-Tooth disease type 1A.
Chinese Journal of Medical Genetics 2020;37(5):578-583
Charcot-Marie-Tooth disease (CMT) is the commonest form of inherited neuropathy and has an incidence of 1/2500. CMT1A is the commonest subtype of CMT, which is caused by duplication of peripheral myelin protein 22 (PMP22) gene and accounts for approximately 50% of CMT diagnosed by genetic testing. Duplication of PMP22 may influence the production of PMP22 mRNA and protein, and interfere with the proliferation, differentiation and apoptosis of Schwann cells. In addition, deregulation of NRG1/ErbB pathway and lipid metabolism can also lead to dysfunction of Schwann cells. Such factors may disturb the myelination process, leading to axon degeneration, muscle weakness, and atrophy subsequently. Accordingly, drug therapies for CMT1A are developed by targeting such factors. PXT3003, antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) are supposed to down-regulate the level of PMP22 mRNA, while recombinant human NRG-1 (rhNRG1) and neurotrophin-3 (NT-3) may enhance Schwann cells survival and differentiation. In addition, lipid-supplemented diet may remedy the defect of lipid metabolism and maintain the proper structure of myelin. Other targeting drugs include ascorbic acid, progesterone antagonists, IFB-088, ADX71441, and ACE-083. This review is to sum up the pathogenesis of CMT1A and promising targeting drug therapies for further research.
Cell Differentiation
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Charcot-Marie-Tooth Disease
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genetics
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pathology
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therapy
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Genetic Testing
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Humans
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Schwann Cells
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cytology
6.PMP22 mutation of an infant-onset Charcot-Marie-Tooth disease family.
Jun-Wei XING ; Ya-Hong LIU ; Bilal Haider SHAMSI ; Xiao-Hong LIU ; Lu TAN ; Man XU
Chinese Journal of Contemporary Pediatrics 2011;13(10):799-803
OBJECTIVETo study the mutation of PMP22 gene of an early-onset family with Charcot-Marie-Tooth disease (CMT) and the genetic features of the disease.
METHODSTwo patients with CMT, fifteen unaffected members in the family and 20 healthy controls were enrolled. STR-PCR and gene scanning were used to detect PMP22 duplication mutation.
RESULTSThe mutations of PMP22 were found in the two patients and other five unaffected members in the family. The mutations were located in the STR locus D17S921 in 5 cases and in the STR locus D17S4A in 2 cases. The other members in the family and 20 healthy controls did not show the mutations of PMP22.
CONCLUSIONSThe gene causing CMT in the family is found in the 17p11.2-p12 region containing PMP22 gene duplication mutation, resulting in the subtype CMT1A.
Charcot-Marie-Tooth Disease ; genetics ; Child ; Child, Preschool ; Chromosomes, Human, Pair 17 ; Female ; Humans ; Male ; Mutation ; Myelin Proteins ; genetics
7.Establishment of L-periaxin gene knock-out RSC96 cell line.
Min LIANG ; Tingting PENG ; Yawei SHI
Chinese Journal of Biotechnology 2016;32(12):1735-1744
Periaxin, a protein of noncompact myelin, is specifically expressed in the peripheral nervous system (PNS). There are two protein isoform L-periaxin and S-Periaxin by alternative splicing of periaxin gene, playing an important role in the initiation of myelin formation. So far, 18 different mutation sites in L-periaxin gene have been found to induce the peripheral demyelinating neurological charcot-marie-tooth diseases subtype 4F (CMT4F). The technique of activation of transcription activator-like effector nucleases (TALENS) was used to knock out the L-periaxin gene in RSC 96 cell line of Rattus. According to the design principle, the knock-out site of L-periaxin was assured to NLS domain of L-periaxin, which is target sequence of left and right arms of TALEN. The knock-out vectors of TALEN-L and TALEN-R were established and transfected into RSC96 cell. After puromycin screening, L-periaxin was knocked out successfully in RSC96 cell, which is confirmed by DNA sequence. The mutation efficiency is 21.6%. S-periaxin, not L-periaxin can be detected by Western blotting in L-periaxin gene knock-out RSC96 cell. The cell growth rate was decreased and the number of cells in G1 increased and decreased in S phase in L-periaxin gene knock-out RSC96 cell by flow cytometry and MTT assay.
Animals
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Cell Line
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Charcot-Marie-Tooth Disease
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genetics
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Gene Knockout Techniques
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Membrane Proteins
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genetics
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Mutation
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Protein Isoforms
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Rats
8.Clinical and genetic analysis of a Chinese family affected with X-linked Charcot-Marie-Tooth disease.
Yapei FENG ; Lin LI ; Xiao LI ; Guilong WANG ; Jiangxia LI ; Qiji LIU
Chinese Journal of Medical Genetics 2013;30(6):659-661
OBJECTIVETo study the clinical manifestations and identify causative mutations for a Chinese family affected with X-linked Charcot-Marie-Tooth disease.
METHODSClinical, electrophysiological and pathological features of the family were carefully analyzed by neurologists. Blood samples were obtained from the proband and other family members. Genomic DNA was extracted. Mutation analysis of GJB1 gene was analyzed with PCR and direct sequencing.
RESULTSThe family has fit with X-linked inheritance, and the affected individuals have typical clinical manifestations. A c.614A>G (p.Asn205Ser) mutation was detected in the GJB1 gene in all affected individuals in the family.
CONCLUSIONA c.614A>G (p.Asn205Ser) mutation of GJB1 gene is co-segregated with the disease phenotype in this family and probably underlies the disease.
Asian Continental Ancestry Group ; genetics ; Charcot-Marie-Tooth Disease ; genetics ; Child ; Connexins ; genetics ; Female ; Genes, X-Linked ; genetics ; Genetic Diseases, X-Linked ; genetics ; Humans ; Male ; Mutation ; Pedigree
9.Identification of a novel c.1A>G variant of GDAP1 gene in a pedigree affected with autosomal recessive fibula atrophy.
Chunlian LIU ; Yousheng YAN ; Junli ZHAO ; Lingxia HA ; Xian XU
Chinese Journal of Medical Genetics 2020;37(11):1244-1246
OBJECTIVE:
To explore the genetic basis for a pedigree affected with Charcot-Marie-Tooth (CMT) disease through high-throughput sequencing.
METHODS:
Potential variants of the genes associated with CMT were screened by next-generation sequencing (NGS) of the members of the pedigree.
RESULTS:
NGS has revealed that the two affected sisters both harbored homozygous c.1A>G variant of the GDAP1 gene, which caused replacement of the first amino acid Methionine by Valine (p.Met1Val). Their parents were both carriers of the heterozygous c.1A>G variant. The variant was unreported previously and has an extremely low frequency in the population. Meanwhile, one of the sisters and the mother also carried heterozygous c.710A>T variant of the BAG3 gene.
CONCLUSION
The homozygous c.1A>G variant of the GDAP1 gene probably underlay the CMT in both children. Above result has enabled clinical diagnosis and genetic counseling for this pedigree.
Adaptor Proteins, Signal Transducing/genetics*
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Apoptosis Regulatory Proteins/genetics*
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Charcot-Marie-Tooth Disease/genetics*
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Child
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Female
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Fibula/abnormalities*
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Homozygote
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Humans
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Mutation
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Nerve Tissue Proteins/genetics*
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Pedigree