Charcot-Marie-Tooth(CMT) disease or hereditary motor and sensory neuropathy is the most common inherited neuromuscular disorder affecting at least 1 in 2500. CMT disease is pathologically and genetically heterogeneous...Charcot-Marie-Tooth(CMT) disease or hereditary motor and sensory neuropathy is the most common inherited neuromuscular disorder affecting at least 1 in 2500. CMT disease is pathologically and genetically heterogeneous and is characterized by a variable age of onset, slowly progressive weakness and muscle atrophy, starting in the lower limbs and subsequently affecting the upper extremities. Symptoms are usually slowly progressive, especially for the classic and late-onset phenotypes, but can be rather severe in early-onset forms. CMT is grouped into demyelinating, axonal and intermediate forms, based on electrophysiological and pathological findings. The demyelinating types are characterized by severely reduced motor nerve conduction velocities(MNCVs) and mainly by myelin abnormalities. The axonal types are characterized by normal or slightly reduced MNCVs and mainly axonal abnormalities. The intermediate types are characterized by MNCVs between 25 m/s and 45 m/s and they have features of both demyelination and axonopathy. Inheritance can be autosomal dominant, X-linked, or autosomal recessive. Mutations in more than 30 genes have been associated with the different forms of CMT, leading to majoradvancements in molecular diagnostics of the disease, as well as in the understanding of pathogenetic mechanisms. This editorial aims to provide an account that is practicable and efficient on the current molecular diagnostic procedures for CMT, in correlation with the clinical, pathological and electrophysiological findings. The most frequent causative mutations of CMT will also be outlined.展开更多
Charcot-Marie-Tooth （CMT） disease is the most common hereditary neuropathy, with a population prevalence of 1 in 2500. CMT disease type 1A （CMT1A）, accounting for ~70% of CMT1 cases and ~ 50% of all CMT cases, is ...Charcot-Marie-Tooth （CMT） disease is the most common hereditary neuropathy, with a population prevalence of 1 in 2500. CMT disease type 1A （CMT1A）, accounting for ~70% of CMT1 cases and ~ 50% of all CMT cases, is transmitted in an autosomal dominant manner. CMT1A maps to chromo- some 17pl 1.2 and is caused, in the majority of cases, by a 1.4- Mb tandem duplication that includes the peripheral myelin protein22 （PMP22） gene （Li et al., 2013）. The disease usually presents in the first 20 years of age, causing difficulty in walking or running, distal symmetrical muscle weakness and wasting, and sensory loss （van Paassen et al., 2014）.展开更多
Background： Among patients with Charcot-Marie-Tooth disease （CMT）, the X-linked variant （CMTX） caused by gap junction protein beta 1 （GJB1） gene mutation is the second most frequent type, accounting for approxi...Background： Among patients with Charcot-Marie-Tooth disease （CMT）, the X-linked variant （CMTX） caused by gap junction protein beta 1 （GJB1） gene mutation is the second most frequent type, accounting for approximately 90% of all CMTX. More than 400 mutations have been identified in the GJB1 gene that encodes connexin 32 （CX32）. CX32 is thought to form gap junctions that promote the diffusion pathway between cells. GJB1 mutations interfere with the formation of the functional channel and impair the maintenance of peripheral myelin, and novel mutations are continually discovered. Methods： We included 79 unrelated patients clinically diagnosed with CMT at the Department of Neurology of the Chinese People＇s Liberation Army General Hospital from December 20, 2012, to December 31, 2015. Clinical examination, nerve conduction studies, and molecular and bioinformatics analyses were performed to identify patients with CMTX 1. Results： Nine GJBI mutations （c.283G〉A, c.77C〉T, c.643C〉T, c.515C〉T, c.191G〉A, c.610C〉T, c.490C〉T, c.491G〉A, and c.44G〉A） were discovered in nine patients. Median motor nerve conduction velocities of all nine patients were 〈 38 m/s, resembling CMT Type 1. Three novel mutations, c.643C〉T, c.191G〉A, and c.610C〉T, were revealed and bioinformatics analyses indicated high pathogenicity. Conclusions： The three novel missense mutations within the GJB1 gene broaden the mutational diversity ofCMT1X. Molecular analysis of family members and bioinformatics analyses of the afflicted patients confirmed the pathogenicity of these mutations.展开更多
文摘Charcot-Marie-Tooth(CMT) disease or hereditary motor and sensory neuropathy is the most common inherited neuromuscular disorder affecting at least 1 in 2500. CMT disease is pathologically and genetically heterogeneous and is characterized by a variable age of onset, slowly progressive weakness and muscle atrophy, starting in the lower limbs and subsequently affecting the upper extremities. Symptoms are usually slowly progressive, especially for the classic and late-onset phenotypes, but can be rather severe in early-onset forms. CMT is grouped into demyelinating, axonal and intermediate forms, based on electrophysiological and pathological findings. The demyelinating types are characterized by severely reduced motor nerve conduction velocities(MNCVs) and mainly by myelin abnormalities. The axonal types are characterized by normal or slightly reduced MNCVs and mainly axonal abnormalities. The intermediate types are characterized by MNCVs between 25 m/s and 45 m/s and they have features of both demyelination and axonopathy. Inheritance can be autosomal dominant, X-linked, or autosomal recessive. Mutations in more than 30 genes have been associated with the different forms of CMT, leading to majoradvancements in molecular diagnostics of the disease, as well as in the understanding of pathogenetic mechanisms. This editorial aims to provide an account that is practicable and efficient on the current molecular diagnostic procedures for CMT, in correlation with the clinical, pathological and electrophysiological findings. The most frequent causative mutations of CMT will also be outlined.
文摘Charcot-Marie-Tooth （CMT） disease is the most common hereditary neuropathy, with a population prevalence of 1 in 2500. CMT disease type 1A （CMT1A）, accounting for ~70% of CMT1 cases and ~ 50% of all CMT cases, is transmitted in an autosomal dominant manner. CMT1A maps to chromo- some 17pl 1.2 and is caused, in the majority of cases, by a 1.4- Mb tandem duplication that includes the peripheral myelin protein22 （PMP22） gene （Li et al., 2013）. The disease usually presents in the first 20 years of age, causing difficulty in walking or running, distal symmetrical muscle weakness and wasting, and sensory loss （van Paassen et al., 2014）.
文摘Background： Among patients with Charcot-Marie-Tooth disease （CMT）, the X-linked variant （CMTX） caused by gap junction protein beta 1 （GJB1） gene mutation is the second most frequent type, accounting for approximately 90% of all CMTX. More than 400 mutations have been identified in the GJB1 gene that encodes connexin 32 （CX32）. CX32 is thought to form gap junctions that promote the diffusion pathway between cells. GJB1 mutations interfere with the formation of the functional channel and impair the maintenance of peripheral myelin, and novel mutations are continually discovered. Methods： We included 79 unrelated patients clinically diagnosed with CMT at the Department of Neurology of the Chinese People＇s Liberation Army General Hospital from December 20, 2012, to December 31, 2015. Clinical examination, nerve conduction studies, and molecular and bioinformatics analyses were performed to identify patients with CMTX 1. Results： Nine GJBI mutations （c.283G〉A, c.77C〉T, c.643C〉T, c.515C〉T, c.191G〉A, c.610C〉T, c.490C〉T, c.491G〉A, and c.44G〉A） were discovered in nine patients. Median motor nerve conduction velocities of all nine patients were 〈 38 m/s, resembling CMT Type 1. Three novel mutations, c.643C〉T, c.191G〉A, and c.610C〉T, were revealed and bioinformatics analyses indicated high pathogenicity. Conclusions： The three novel missense mutations within the GJB1 gene broaden the mutational diversity ofCMT1X. Molecular analysis of family members and bioinformatics analyses of the afflicted patients confirmed the pathogenicity of these mutations.
