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 >70 genes. 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 such that we will enroll >5000 patients into our protocols by the end of our initial five year cycle. We have developed a Web Page that provides information to patients, families and investigators. It also has allowed us to directly interact with patients through our INC Contact Registry and have developed the CMT-lnternational 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, and to provide information to patients, families and investigators through our INC Website.

Public Health Relevance

The overview provides a description of the groups of inherited neuropathies covered in the INC RDCRC and the INC scientific and administrative leadership and multidisciplinary team that comprise the consortium. We discuss the goals and objectives of the projects, describe the role of the INC Patient Advocacy Groups and both INC Website and research environment. Our plans to generate a central IRB and our progress during the previous cycle are also presented.

National Institute of Health (NIH)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZTR1)
Program Officer
Gwinn, Katrina
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
Dortch, Richard D; Dethrage, Lindsey M; Gore, John C et al. (2014) Proximal nerve magnetization transfer MRI relates to disability in Charcot-Marie-Tooth diseases. Neurology 83:1545-53
Brewer, Megan Hwa; Ma, Ki Hwan; Beecham, Gary W et al. (2014) Haplotype-specific modulation of a SOX10/CREB response element at the Charcot-Marie-Tooth disease type 4C locus SH3TC2. Hum Mol Genet 23:5171-87
Lam, Byron L; Züchner, Stephan L; Dallman, Julia et al. (2014) Mutation K42E in dehydrodolichol diphosphate synthase (DHDDS) causes recessive retinitis pigmentosa. Adv Exp Med Biol 801:165-70
Finkel, Richard S; McDermott, Michael P; Kaufmann, Petra et al. (2014) Observational study of spinal muscular atrophy type I and implications for clinical trials. Neurology 83:810-7
Liu, Yo-Tsen; Laurá, Matilde; Hersheson, Joshua et al. (2014) Extended phenotypic spectrum of KIF5A mutations: From spastic paraplegia to axonal neuropathy. Neurology 83:612-9
Mudge, Anita J; Bau, Karen V; Purcell, Leanne N et al. (2014) Normative reference values for lower limb joint range, bone torsion, and alignment in children aged 4-16 years. J Pediatr Orthop B 23:15-25
Foley, A Reghan; Menezes, Manoj P; Pandraud, Amelie et al. (2014) Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2. Brain 137:44-56
Ramchandren, Sindhu; Jaiswal, Mamta; Feldman, Eva et al. (2014) Effect of pain in pediatric inherited neuropathies. Neurology 82:793-7
Wen, Rong; Dallman, Julia E; Li, Yiwen et al. (2014) Knock-down DHDDS expression induces photoreceptor degeneration in zebrafish. Adv Exp Med Biol 801:543-50
Griffin, Laurie B; Sakaguchi, Reiko; McGuigan, David et al. (2014) Impaired function is a common feature of neuropathy-associated glycyl-tRNA synthetase mutations. Hum Mutat 35:1363-71

Showing the most recent 10 out of 53 publications