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1.
Varying degrees of optic neuropathy can be seen in patients with Charcot–Marie–Tooth (CMT) disease. To define and characterize the extent of optic neuropathy in patients with CMT2A and CMT1A, two patients from both sub-classifications were evaluated. All patients underwent complete neuro-ophthalmic examinations, and optical coherence (OCT) measurements of the retinal nerve fiber layer (RNFL) and ganglion cell layer complex (GCC) were obtained, along with pattern visual evoked potential (VEP) and pattern electroretinogram (ERG) recordings. RNFL thickness measurements were decreased in both patients with CMT2A, and normal in both patients with CMT1A. GCC measurements were decreased in both patients with CMT2A, mildly decreased in one patient with CMT1A and normal in the second CMT1A patient. VEP latencies were delayed in one patient with CMT2A and one patient with CMT1A. VEP latencies were immeasurable in the other CMT2A patient and not obtained in the second CMT1A patient. Pattern ERG P50-N95 amplitudes were decreased in both patients with CMT2A and normal in one patient with CMT1A. The pattern ERG was immeasurable in the second patient with CMT1A. The pattern of RNFL and GCC thinning in CMT2A with optic neuropathy, a subset of HMSN VI, closely resembles that seen in other mitochondrial optic neuropathies. 相似文献
2.
Yasuo Miki Masahiko Tomiyama Rie Haga Haruo Nishijima Chieko Suzuki Aiichiro Kurihara Kazuhiro Sugimoto Akihiro Hashiguchi Hiroshi Takashima Masayuki Baba 《Journal of neurology》2013,260(4):1147-1151
We report a family of intravenous immunoglobulin (IVIg)-responsive X-linked Charcot–Marie–Tooth disease Type 1 (CMT1X) with a novel gap junction protein 1 mutation. Two of three siblings in the family complained of subacute motor and sensory impairment, and their symptoms improved after the administration of IVIg. Additional IVIg treatment also resulted in similar improvement. The other also showed a mild improvement on IVIg. It has been suggested that an immune-mediated process is involved in the progression of neuropathy in CMT1X. The finding in our report provides evidence of susceptibility to immune-mediated demyelinating neuropathy in some form of CMT1X. Superimposed demyelinating neuropathy as well as a gradual deterioration of neuropathy over decades can be a clinical manifestation of CMT1X. 相似文献
3.
17p duplicated Charcot–Marie–Tooth 1A 总被引:1,自引:0,他引:1
Marques W Freitas MR Nascimento OJ Oliveira AB Calia L Melo A Lucena R Rocha V Barreira AA 《Journal of neurology》2005,252(8):972-979
The most frequent
type of Charcot–Marie–Tooth
(CMT) neuropathy is that associated
with the 17p11.2–p12 chromosome
duplication, whose characteristics
have been well described in
European and North American
populations. In this study, we analyzed
a Brazilian population exhibiting
the mutation, found in 57
patients from 42 families (79%) of
a cohort of 53 families with demyelinating
CMT. Almost 20% of
the duplicated cases were sporadic.
In 77% of the duplicated families
the mutation event occurred in the
hot spot area of the CMT1A–Rep
region. Forty–five percent of patients
were females, 84% were Caucasians
and 13% of African descent.
Distal limb weakness was the
most frequent abnormality, appearing
in 84% of patients, although
uncommon manifestations
such as severe proximal weakness,
floppy baby syndrome, diaphragmatic
weakness and severe scoliosis
were also observed. One patient
was wheelchair–bound, and three
suffered severe hand weakness.
Sensory abnormalities were detected
in 84% of the cases, but 80%
were unaware of this impairment.
Twelve patients complained of positive
sensory manifestations such
as pain and paresthesias. Progression
was reported by 40%. Motor
conduction velocities in the upper
limbs were always less than 35 m/s,
and less than 30.4 m/s in the peroneal
nerve. The findings of this
study expand the clinical spectrum
of the disease. 相似文献
4.
Charcot–Marie–Tooth disease (CMT) is the most frequent form of inherited neuropathy with great variety of phenotypes, inheritance patterns, and causative genes. According to median motor nerve conduction velocity (MNCV), CMT is divided into demyelinating (CMT1) with MNCV below 38 m/s, axonal (CMT2) with MNCV above 38 m/s, and intermediate CMT with MNCV between 25 and 45 m/s. In each category, transmission may be autosomal dominant, autosomal recessive, or X-linked. The nosology of intermediate CMT is controversial because of concerns about electrophysiological delimitation. A systematic computer-based literature search was conducted on PubMed, using the following MeSH: (1) intermediate Charcot–Marie–Tooth; (2) X-linked intermediate Charcot–Marie–Tooth; and (3) X-linked Charcot–Marie–Tooth and electrophysiology. We retrieved 225 articles reporting X-linked CMT or intermediate CMT with electrophysiological information. After eligibility, 156 papers were used for this review. In assessing median MNCV, compound muscle action potential (CMAP) amplitudes were taken into account. In cases with attenuated CMAP and wherever possible, proximal median MNCV was used for accurate definition of conduction slowing in the intermediate range. In the vast majority of males with X-linked CMT associated with GJB1 mutation (CMTX1), median MNCV was intermediate. CMT associated with DRP2 mutation is another well-documented X-linked intermediate disorder. Autosomal dominant intermediate CMT (DI-CMT) encompasses 11 different types; six of them with assigned phenotype MIM number and the remaining five being unnumbered. Based on available electrophysiological information, we wonder if DI-CMTA should be reclassified within CMT2. Autosomal recessive intermediate CMT (RI-CMT) covers four numbered MIM phenotypes though, in accordance with reported electrophysiology, two of them (RI-CMTB and RI-CMTD) should probably be reclassified within AR-CMT2. We conclude that intermediate CMT is a complex inherited syndrome, whose characterization requires a specific electrophysiological protocol comprising evaluation of upper limb proximal nerve trunks when distal CMAP amplitudes are reduced, and that an updated version of MIM phenotype numbering is needed. 相似文献
5.
Clinical and electrophysiological characteristics of women with X-linked Charcot–Marie–Tooth disease
Luce Barbat du Closel Nathalie Bonello-Palot Yann Péréon Andoni Echaniz-Laguna Jean Philippe Camdessanche Aleksandra Nadaj-Pakleza Jean-Baptiste Chanson Simon Frachet Laurent Magy Julien Cassereau Pascal Cintas Ariane Choumert Perrine Devic Sarah Leonard Louis Robinson Gravier Dumonceau Emilien Delmont Emmanuelle Salort-Campana Françoise Bouhour Philippe Latour Tanya Stojkovic Shahram Attarian 《European journal of neurology》2023,30(10):3265-3276
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Lorena Lorefice Maria Rita Murru Giancarlo Coghe Giuseppe Fenu Daniela Corongiu Jessica Frau Stefania Tranquilli Paolo Tacconi Alessandro Vannelli Giovanni Marrosu Elena Mamusa Eleonora Cocco Maria Giovanna Marrosu 《Neurological sciences》2017,38(6):1019-1025
Charcot–Marie–Tooth disease (CMT) is characterised by great variability of genetic subtypes. This study aimed to assess the genetic subtypes of CMT disease in the Sardinian population. Genetic screening was performed for CMT cases (CMT1, CMT2, and hereditary neuropathy with susceptibility to pressure palsies [HNPP]). A total of 1,043 subjects (119 index cases) were evaluated. In CMT1 index cases (69/119; 58%), PMP22 duplication at 17p11.2 was the most frequent genetic diagnosis (60/69; 87%), followed by mutations in the GJB1 gene (5/69; 7.2%), in the SH3TC2 gene (3/69; 4.4%) and PMP22 Gly107Val point mutation (1/69; 1.4%). The CMT2 group (24/119; 20.1%) comprised 10/24 (41.6%) patients carrying MPZ gene Ser44Phe mutation, 6/24 (25%) with mutations in MFN2 and HSPB1, and 1/24 (4.2%) in GJB1 and LRSAM1. In the HNPP group (26/119; 21.9%), the majority of patients reported the PMP22 deletion (25/26; 96.2%). Further studies are needed to comprehend the overall picture of the disease in Mediterranean area. 相似文献
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9.
Shoko Tokunaga Akihiro Hashiguchi Akiko Yoshimura Kengo Maeda Takashi Suzuki Hiroyo Haruki Tomonori Nakamura Yuji Okamoto Hiroshi Takashima 《Neurogenetics》2012,13(4):359-365
We identified the main features of Charcot–Marie–Tooth (CMT) disease, type 4F, caused by a periaxin gene (PRX) mutation in Japanese patients. Periaxin is known as one of the key myelination molecules, forming tight junction between myelin loop and axon. We collected 427 DNA samples from individuals with CMT or CMT-related neuropathy, negative for PMP22 duplication. We investigated PRX mutations using a purpose-built resequencing array screen during the period 2006–2012. We detected two types of PRX mutations in three patients; one patient showed a novel homozygous p.D651N mutation and the other two showed homozygous p.R1070X mutation. All PRX mutations reported so far have been of nonsense or frameshift type. In this study, we found homozygous missense mutation p.D651N. Aspartate 651 is located in a repeat domain; its position might indicate an important function. PRX mutations usually lead to early-onset, autosomal-recessive demyelinating CMT neuropathy 4F (CMT4F) or Dejerine–Sottas disease; their clinical phenotypes are severe. In our three patients, the onset of the disease was at the age of 27?years or later, and their clinical phenotypes were milder compared with those reported in previous studies. We showed a variation of clinical phenotypes for CMT4F caused by a novel, nonsense PRX mutation. 相似文献
10.
Noriko Nishikura Takanori Yamagata Takao Morimune Jun Matsui Tatsuyuki Sokoda Chihiro Sawai Yuko Sakaue Yujiro Higuchi Akihiro Hashiguchi Hiroshi Takashima Yoshihiro Takeuchi Yoshihiro Maruo 《Brain & development》2019,41(2):201-204
X-linked Charcot–Marie–Tooth disease type 5 (CMTX5) is an X-linked disorder characterized by early-onset sensorineural hearing impairment, peripheral neuropathy, and progressive optic atrophy. It is caused by a loss-of-function mutation in the phosphoribosyl pyrophosphate synthetase 1 gene (PRPS1), which encodes isoform I of phosphoribosyl pyrophosphate synthetase (PRS-I). A decreased activity leads to nonsyndromic sensorineural deafness (DFN2), CMTX5, and Arts syndrome depending upon residual PRS-I activity. Clinical and neurophysiological features of pediatric CMTX5 are poorly defined. We report two male siblings with peripheral neuropathy and prelingual sensorineural hearing loss who carried a novel c.319A>G (p.Ile107Val) PRPS1 missense mutation. They exhibited recurrent episodes of transient proximal muscle weakness, showing Gowers’ sign and waddling gait after suffering from febrile illness. This transient weakness has not been previously reported in CMTX5. A patient with Arts syndrome was reported to have transient proximal weakness after febrile illness. The transient weakness presenting in both CMTX5 and Arts syndrome suggests an overlap of signs and a continuous spectrum of PRS-I hypoactivity disease. Children presenting with transient neurological signs should be evaluated for peripheral neuropathy and consider genetic analysis for PRPS1. 相似文献
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Rare copy number variations by the nonrecurrent rearrangements involving PMP22 have been recently suggested to be associated with CMT1A peripheral neuropathy. As a mechanism of the nonrecurrent rearrangement,
replication-based fork stalling template switching (FoSTeS) by microhomology-mediated break-induced replication (MMBIR) has
been proposed. We found three Korean CMT1A families with putative nonrecurrent duplication. The duplications were identified
by microsatellite typing and applying a CGH microarray. The breakpoint sequences in two families suggested an Alu–Alu-mediated rearrangement with the FoSTeS by the MMBIR, and a two-step rearrangement of the replication-based FoSTeS/MMBIR and
meiosis-based recombination. The two-step mechanism has still not been reported. Segregation analysis of 17p12 microsatellite
markers and breakpoint junction analysis suggested that the nonrecurrent rearrangements are stably inherited without alteration
of junction sequence; however, they may allow some alteration of the genomic contents in duplication across generations by
recombination event. It might be the first study on the pedigree analysis of the large CMT1A families with nonrecurrent rearrangements.
It seems that the exact mechanism of the nonrecurrent rearrangements in the CMT1A may have a far more complex process than
has been expected. 相似文献
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14.
Neurotoxicity is a common side effect of vincristine (VCR) treatment. Severe exacerbations of neuropathy have been reported
in patients with Charcot–Marie–Tooth disease (CMT) 1A with duplication of the peripheral myelin protein 22 (PMP22) gene. However, whether or not VCR exacerbates neuropathies through mutations in other CMT-associated genes besides PMP22 duplication has not been well studied. The purpose of this study was to identify mutations in any CMT-associated genes in
a patient with hypersensitivity to VCR. We performed clinical, electrophysiological, and genetic examinations of a 23-year-old
woman, who was hypersensitive to low-dose VCR, and her healthy mother. DNA analysis was performed using our specially designed
resequencing array that simultaneously screens for 28 CMT-associated genes. Electrophysiological studies revealed that the
patient and her healthy mother had demyelinating polyneuropathy. Furthermore, they showed the same novel mutation in the early growth response 2 (EGR2) gene. Recognizing pre-existing asymptomatic CMT by electrophysiological studies and genetic analysis before VCR treatment
allowed us to prevent severe VCR-induced neuropathy. 相似文献
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16.
Charcot–Marie–Tooth causing HSPB1 mutations increase Cdk5-mediated phosphorylation of neurofilaments
Anne Holmgren Delphine Bouhy Vicky De Winter Bob Asselbergh Jean-Pierre Timmermans Joy Irobi Vincent Timmerman 《Acta neuropathologica》2013,126(1):93-108
Mutations in the small heat shock protein HSPB1 (HSP27) are a cause of axonal Charcot–Marie–Tooth neuropathy (CMT2F) and distal hereditary motor neuropathy. To better understand the effect of mutations in HSPB1 on the neuronal cytoskeleton, we stably transduced neuronal cells with wild-type and mutant HSPB1 and investigated axonal transport of neurofilaments (NFs). We observed that mutant HSPB1 affected the binding of NFs to the anterograde motor protein kinesin, reducing anterograde transport of NFs. These deficits were associated with an increased phosphorylation of NFs and cyclin-dependent kinase Cdk5. As Cdk5 mediates NF phosphorylation, inhibition of Cdk5/p35 restored NF phosphorylation level, as well as NF binding to kinesin in mutant HSPB1 neuronal cells. Altogether, we demonstrate that HSPB1 mutations induce hyperphosphorylation of NFs through Cdk5 and reduce anterograde transport of NFs. 相似文献
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18.
Charcot–Marie–Tooth disease (CMT), which is the eponym for hereditary motor and sensory neuropathy (HMSN), affects ~1 in 2500 individuals. The most common subtype of X-linked CMT, CMTX1, is caused by mutations in GJB1, the gene encoding connexin 32, a gap junction protein in myelinated Schwann cells. We report a woman, who presented at the age of 56 years with gait unsteadiness and tingling in her feet. Clinical investigation revealed impaired sensation to pinprick, light touch and vibration in her distal lower limbs. Ankle reflexes were bilaterally absent. Sequencing revealed a novel heterozygous c.712C>T (p.R238C) mutation in the GJB1 gene. This mutation is predicted to result in the loss of disulfide bonds and thus in abnormal protein structure. In this woman, the reported novel GJB1 mutation resulted in sensory abnormalities, slowly progressive loss of distal lower limb strength, and notable loss of balance, with onset of symptoms late in adult age. 相似文献
19.
Vengalathur Ganesan Ramesh 《中国神经再生研究》2014,9(8):877-877
<正>To the editor,I read with interest the article,"Differences in individual susceptibility affect the development of trigeminal neuralgia"by Duransoy et al.(2013).The authors have analyzed the possible pathogenesis of trigeminal neuralgia,with illustrative case examples.They have drawn very important conclusions,which may have implications in 相似文献