The various rare forms of hereditary peripheral neuropathies are known as Charcot-Marie-Tooth (CMT) disease and comprise a clinically and genetically heterogeneous set of neurological disorders. Traditionally, the disease is divided into demyelinating CMT1 forms with decreased nerve conduction velocities (NCV) and axonal CMT2 types with normal NCVs. More than 35 different genes have been identified for CMT and include autosomal dominant, recessive and X-linked forms. Still, only 40% of axonal (CMT2) cases currently have a mutation in one of the known genes. Importantly, the degree of phenotypic variation of severity, age-at-onset, and other measures within families is quite remarkable, yet genetic modifying factors have not been identified. Modifying factors in CMT families are likely targets for intervention and may well be important for other non-hereditary peripheral neuropathies, such as diabetic neuropathy. These studies have proven difficult however, primarily due to a lack of collections of patients with consistent clinical evaluations and their DNA. The proposed Rare Diseases Clinical Research Consortia (RDCRC) will substantially enhance our resources and quickly provide a large number of CMT patients and families evaluated with the same clinical severity score. A new generation of genetic tools is now available to tackle these important questions, such as genome-wide association studies and next-generation sequencing technology. These will also be applied to identify additional CMT2 genes in small pedigrees using innovative approaches.
| Hu, Bo; McCollum, Megan; Ravi, Vignesh et al. (2018) Myelin abnormality in Charcot-Marie-Tooth type 4J recapitulates features of acquired demyelination. Ann Neurol 83:756-770 |
| Dankwa, Lois; Richardson, Jessica; Motley, William W et al. (2018) A mutation in the heptad repeat 2 domain of MFN2 in a large CMT2A family. J Peripher Nerv Syst 23:36-39 |
| Bai, Yunhong; Wu, Xingyao; Brennan, Kathryn M et al. (2018) Myelin protein zero mutations and the unfolded protein response in Charcot Marie Tooth disease type 1B. Ann Clin Transl Neurol 5:445-455 |
| Rebelo, Adriana P; Saade, Dimah; Pereira, Claudia V et al. (2018) SCO2 mutations cause early-onset axonal Charcot-Marie-Tooth disease associated with cellular copper deficiency. Brain 141:662-672 |
| Abbott, Jamie A; Meyer-Schuman, Rebecca; Lupo, Vincenzo et al. (2018) Substrate interaction defects in histidyl-tRNA synthetase linked to dominant axonal peripheral neuropathy. Hum Mutat 39:415-432 |
| Abrams, Alexander J; Fontanesi, Flavia; Tan, Natalie B L et al. (2018) Insights into the genotype-phenotype correlation and molecular function of SLC25A46. Hum Mutat 39:1995-2007 |
| Sandelius, Åsa; Zetterberg, Henrik; Blennow, Kaj et al. (2018) Plasma neurofilament light chain concentration in the inherited peripheral neuropathies. Neurology 90:e518-e524 |
| Lassuthova, Petra; Rebelo, Adriana P; Ravenscroft, Gianina et al. (2018) Mutations in ATP1A1 Cause Dominant Charcot-Marie-Tooth Type 2. Am J Hum Genet 102:505-514 |
| Panosyan, Francis B; Kirk, Callyn A; Marking, Devon et al. (2018) Carpal tunnel syndrome in inherited neuropathies: A retrospective survey. Muscle Nerve 57:388-394 |
| Synofzik, Matthis; Helbig, Katherine L; Harmuth, Florian et al. (2018) De novo ITPR1 variants are a recurrent cause of early-onset ataxia, acting via loss of channel function. Eur J Hum Genet 26:1623-1634 |
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