The inherited neuropathy consortium (INC) will investigate Charcot-Marie-Tooth disease (CMT), a heterogeneous group of inherited neurological disorders affecting ~1 in 2,500 people [1, 2]. Over the last 2 decades there have been major advances in identifying the causative genes for CMT with >30 genes already described. These are typically grouped into dominantly inherited demyelinating neuropathies (CMT1), dominantly inherited axonal neuropathies (CMT2) and recessively inherited neuropathies (CMT4). An investigation of these three groups is the focus of the INC, our RDCRC. Extensive progress in understanding the pathogenesis of inherited neuropathies has occurred but there are still no effective treatments for any form of CMT [3-5] and the first large scale therapeutic trials for CMT1A (the commonest form of CMT) are only now underway (Shy, Herrmann, Me Dermott and Reilly, members of the INC, are involved in these trials). Research into CMT is therefore at a critical point where the laboratory based basic science discoveries are beginning to be translated into treatments for patients (bench to bedside model). However, there remain major obstacles to the effective translation of these basic science discoveries into treatments including (1) the lack of widespread expertise in diagnosis and management of CMT, (2) the lack of accepted uniform methods of clinically analyzing different kinds of patients with CMT (including the lack of tools specifically designed for inherited neuropathy patients e.g. nerve imaging, disease biomarkers), (3), the lack of a disability or impairment scales to monitor children with CMT and the need to continually improve the current accepted CMT neuropathy score (CMTNS) [6] for monitoring adults, (4), the lack of natural history studies in most forms of CMT including CMT1B, CMT2A and CMT4A, (5), the lack of information of genetic modifiers of all forms of CMT, and finally, (6), the lack of trained inherited neuropathy trial physicians to conduct clinical trials in CMT. Among the most important of these needs is to specifically train neurologists interested in peripheral neuropathies for clinical research in inherited neuropathies. To date most neuromuscular fellowships are directed towards acquired neuropathies such as diabetes, inflammatory neuropathies and painful small fiber neuropathies as these are more common and have been more treatable to date. Although inherited neuropathies may be a small component of these fellowships we feel it is essential to specifically train neurologists to both understand the genetics, clinical presentation and physiology of the various forms of CMT and also to enable young investigators to conduct high level clinical research in the inherited neuropathies. Our ideal trainees would typically have completed a neuromuscular fellowship (or equivalent) and either be at advanced post-doctoral or junior faculty levels who wish to develop a clinical research career into inherited neuropathies. Senior specialist registrars (SPRs) in neurology would be at an equivalent developmental position in the UK. An ideal training program should be comprehensive and flexible (as outlined below) to train investigators in all forms of clinical research including research methods for clinical assessment and natural history studies (including clinical pattern recognition, neurophysiologic methodologies, neuromuscular imaging and nerve pathology), and the development expertise in clinical trial design and biostatistics. For select candidates, clinically related laboratory based research should also be possible
| 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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