The Inherited Neuropathy Consortium (INC) RDCRC is a network of clinical investigators dedicated to developing the infrastructure necessary to evaluate therapies for patients with heritable peripheral neuropathies, collectively known as Charcot-Marie-Tooth disease (CMT). Originally, the INC consisted of six sites. Supplemental funding from the Muscular Dystrophy Association (MDA) and Charcot Marie Tooth Association (CMTA) has allowed us to expand to 17 sites. CMT is caused by mutations in >80 genes, 15 of which have been identified by INC sites over the past 5 years. Mutations cause dominantly inherited demyelinating CMT (CMT1), dominantly inherited axonal CMT (CMT2), and recessively inherited CMT (CMT4). Despite scientific advances there are currently no medications to slow progression for any form. In part this is due to the lack of adequate natural history data, the lack of sensitive outcome measures and the lack of biomarkers for CMT. In addition, there has not been a coordinated international effort to share clinical data on patients. We have addressed these areas during our initial cycle of the INC. We have performed natural history studies, generated and tested outcome instruments for adults and children with CMT, and begun testing potential biomarkers. We have developed patient reported outcome (PRO) instruments. We have worked as an international group that has enrolled > 6500 participants into our protocols at the time of this submission. We have developed a Web Page that provides information to patients, families and investigators. It also has allowed us to directly interact wih patients through our INC Contact Registry and have developed the CMT-International Database (CMT-ID), that consists of national registries from around the world that use the same CMT Minimal Dataset that is used by the INC. Finally, we have trained a number of young investigators who are committed to a career investigating CMT. In our second cycle we propose Aims to extend our natural history data, to extend our Next Generation Sequencing data, to identify potential biomarkers and outcome measures, to perform clinical trials, begin developing Standards of Care for people with CMT and to provide information to patients, families and investigators through our INC Website.

Public Health Relevance

The overall section provides a description of the groups of inherited neuropathies covered in the INC RDCRC, how they are separated into three target groups and the rational for our international consortium. We describe the multidisciplinary team, including Patient Advocacy Groups (PAGS) that comprise the consortium. Finally, we describe our plans to maintain a state of the art Website, to develop a central IRB through IRBshare and we review our achievements during the past grant cycle as well as our goals and objectives going forward.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel ()
Program Officer
Nuckolls, Glen H
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Iowa
Schools of Medicine
Iowa City
United States
Zip Code
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, ├ůsa; 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
Shy, Michael E (2018) Antisense oligonucleotides offer hope to patients with Charcot-Marie-Tooth disease type 1A. J Clin Invest 128:110-112
Jerath, Nivedita U; Mankodi, Ami; Crawford, Thomas O et al. (2018) Charcot-Marie-Tooth Disease type 4C: Novel mutations, clinical presentations, and diagnostic challenges. Muscle Nerve 57:749-755
Tomaselli, Pedro J; Horga, Alejandro; Rossor, Alexander M et al. (2018) IGHMBP2 mutation associated with organ-specific autonomic dysfunction. Neuromuscul Disord 28:1012-1015
Johnson, Nicholas E; Heatwole, Chad; Creigh, Peter et al. (2018) The Charcot-Marie-Tooth Health Index: Evaluation of a Patient-Reported Outcome. Ann Neurol 84:225-233
Davies, Jenny L; Engelstad Sr.,, Janean K; E Gove, Linde et al. (2018) Somatotopic heat pain thresholds and intraepidermal nerve fibers in health. Muscle Nerve 58:509-516

Showing the most recent 10 out of 189 publications