Epidemiologic Study of Charcot-Marie-Tooth Disease: A Systematic Review

Background: Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy. CMT is classified into 2 main subgroups: CMT type 1 (CMT1; demyelinating form) and CMT type 2 (CMT2; axonal form). The objectives of this study were to systematically review and assess the quality of studies reporting the incidence and/or prevalence of CMT worldwide. Summary: A total of 802 studies were initially identified, with only 12 meeting the inclusion criteria. CMT prevalence was reported in 10 studies and ranged from 9.7/100,000 in Serbia to 82.3/100,000 in Norway. The frequency of the main subtypes varied from 37.6 to 84% for CMT1 and from 12 to 35.9% for CMT2; the country with the lowest prevalence of CMT1 was Norway, and the country with the highest prevalence of CMT1 was Iceland; on the other hand, CMT2 was least prevalent in the United Kingdom and most prevalent in Norway. Key Messages: This review reveals the gaps that still exist in the epidemiological knowledge of CMT around the world. Published studies are of varying quality and utilise different methodologies, thus precluding a robust conclusion. Additional research focusing on epidemiological features of CMT in different nations and different ethnic groups is needed.

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Rapid detection of a recombinant hotspot associated with Charcot–Marie–Tooth disease type 1A duplication by a PCR-based DNA test

Clinical Chemistry ◽

10.1093/clinchem/44.2.270 ◽

1998 ◽

Vol 44 (2) ◽

pp. 270-274 ◽

Cited By ~ 6

Author(s):

Jan-Gowth Chang ◽

Yuh-Jyh Jong ◽

Wen-Pin Wang ◽

Jyh-Chwan Wang ◽

Chaur-Jong Hu ◽

...

Keyword(s):

Rapid Detection ◽

Disease Type ◽

Chinese Patients ◽

Charcot Marie Tooth ◽

Dna Test ◽

Charcot Marie Tooth Disease ◽

Repeat Sequences ◽

Tooth Disease

Abstract A 1.5-Mb duplication on chromosome 17p11.2-p12 (CMT1A duplication) caused by a misalignment of the CMT1A repeat sequences (CMT1A-REPs) is associated with Charcot–Marie–Tooth disease type 1A (CMT1A). A hotspot of crossover breakpoints located in a 3.2-kb region of the CMT1A-REPs accounts for three-quarters of the rearrangements in CMT1A patients. We developed a PCR-based diagnostic method to detect a recombination hotspot associated with the CMT1A duplication. Thirty-one CMT1A Chinese patients from different families and 50 healthy people over 65 years of age were studied. Twenty-seven of the 31 cases demonstrated the 3.2-kb hotspot crossover, of which there were two subgroups. The type 1 crossover breakpoint was located at the distal CMT1A-REP around the PmeI site, and accounted for 24 of the 27 cases with a 3.2-kb hotspot crossover in CMT1A duplication patients. The type 2 crossover breakpoint was located at the distal CMT1A-REP around the base 3625 region, accounting for 3 of the 27 cases. The results correlated very well with the results of Southern transfer analysis. This study has a potentially important role in the diagnosis of CMT1A disease.

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Adaptation by alternative RNA splicing of slow troponin T isoforms in type 1 but not type 2 Charcot-Marie-Tooth disease

AJP Cell Physiology ◽

10.1152/ajpcell.00110.2008 ◽

2008 ◽

Vol 295 (3) ◽

pp. C722-C731 ◽

Cited By ~ 11

Author(s):

Lars Larsson ◽

Xin Wang ◽

Fushun Yu ◽

Peter Höök ◽

Kristian Borg ◽

...

Keyword(s):

Molecular Weight ◽

Muscle Function ◽

Rna Splicing ◽

Troponin T ◽

Charcot Marie Tooth ◽

Charcot Marie Tooth Disease ◽

Form Type ◽

Tooth Disease

Slow troponin T (TnT) plays an indispensable role in skeletal muscle function. Alternative RNA splicing in the NH2-terminal region produces high-molecular-weight (HMW) and low-molecular-weight (LMW) isoforms of slow TnT. Normal adult slow muscle fibers express mainly HMW slow TnT. Charcot-Marie-Tooth disease (CMT) is a group of inherited peripheral polyneuropathies caused by various neuronal defects. We found in the present study that LMW slow TnT was significantly upregulated in demyelination form type 1 CMT (CMT1) but not axonal form type 2 CMT (CMT2) muscles. Contractility analysis showed an increased specific force in single fibers isolated from CMT1 but not CMT2 muscles compared with control muscles. However, an in vitro motility assay showed normal velocity of the myosin motor isolated from CMT1 and CMT2 muscle biopsies, consistent with their unchanged myosin isoform contents. Supporting a role of slow TnT isoform regulation in contractility change, LMW and HMW slow TnT isoforms showed differences in the molecular conformation in conserved central and COOH-terminal regions with changed binding affinity for troponin I and tropomyosin. In addition to providing a biochemical marker for the differential diagnosis of CMT, the upregulation of LMW slow TnT isoforms under the distinct pathophysiology of CMT1 demonstrates an adaptation of muscle function to neurological disorders by alternative splicing modification of myofilament proteins.

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Disability and quality of life in Charcot-Marie-Tooth disease type 1

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp.70.4.548 ◽

2001 ◽

Vol 70 (4) ◽

pp. 548-550 ◽

Cited By ~ 43

Author(s):

G Pfeiffer

Keyword(s):

Quality Of Life ◽

Disease Type ◽

Charcot Marie Tooth ◽

Charcot Marie Tooth Disease ◽

Tooth Disease

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Squalenoyl siRNA PMP22 nanoparticles are effective in treating mouse models of Charcot-Marie-Tooth disease type 1 A

Communications Biology ◽

10.1038/s42003-021-01839-2 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Suzan Boutary ◽

Marie Caillaud ◽

Mévidette El Madani ◽

Jean-Michel Vallat ◽

Julien Loisel-Duwattez ◽

...

Keyword(s):

Mouse Models ◽

Disease Type ◽

Major Step ◽

Charcot Marie Tooth ◽

Charcot Marie Tooth Disease ◽

Protein Levels ◽

Positive Effects ◽

Severity Of The Disease ◽

Tooth Disease

AbstractCharcot-Marie-Tooth disease type 1 A (CMT1A) lacks an effective treatment. We provide a therapy for CMT1A, based on siRNA conjugated to squalene nanoparticles (siRNA PMP22-SQ NPs). Their administration resulted in normalization of Pmp22 protein levels, restored locomotor activity and electrophysiological parameters in two transgenic CMT1A mouse models with different severity of the disease. Pathological studies demonstrated the regeneration of myelinated axons and myelin compaction, one major step in restoring function of myelin sheaths. The normalization of sciatic nerve Krox20, Sox10 and neurofilament levels reflected the regeneration of both myelin and axons. Importantly, the positive effects of siRNA PMP22-SQ NPs lasted for three weeks, and their renewed administration resulted in full functional recovery. Beyond CMT1A, our findings can be considered as a potent therapeutic strategy for inherited peripheral neuropathies. They provide the proof of concept for a new precision medicine based on the normalization of disease gene expression by siRNA.

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