Charcot Marie Tooth disease (CMT) is the eponym for heritable peripheral neuropathy. These are among the most common inherited neuromuscular diseases, affecting approximately 1 in 2500 people. Mutations in more than 30 genes cause CMT, and loci for more than 40 additional genes have been identified. CMT is separable into three specific groups: (1) CMT1, dominantly inherited demyelinating neuropathies;(2) CMT2, dominantly inherited axonal neuropathies;and (3) CMT4, recessively inherited neuropathies. Genetically authentic animal models exist for many forms of CMT, and have provided the data compelling the clinical trials in humans that are currently underway for CMT1 A. Despite these advances, no effective therapies are available for any form of CMT, natural history data are available for only the most common types (CMT1A and CMT1X), and many potential genotype-phenotype correlations remain unknown. To address these issues, we have created the Hereditary Neuropathy Consortium (HNC), a collection of clinical researchers with demonstrated expertise in CMT. Sites within the HNC include Wayne State University, the National Hospital for Neurology/Neurosurgery in London, the University of Rochester/Muscle Study Group (MSG), the University of Pennsylvania/Children's Hospital of Philadelphia (CHOP), and the University of Miami, Florida. Two Pilot Projects will be performed. Dr. Gyula Acsadi from WSU will develop a Pediatric Scoring System for CMT patients, aided by Dr. Muntoni from London and Dr. Finkel from CHOP. Dr. Scherer will develop a Website patterned after OMIM for patients and researchers interested in CMT. Two Clinical Research Projects will be performed. Dr. Shy, from WSU, will undertake a natural history analysis of CMT1B, CMT2A, and CMT4A. Drs Zuchner and Vance, from Miami, will perform a search for modifier genes in various forms of CMT. Dr. Mary Reilly from London will lead a training program for postdoctoral fellows and junior faculty members that will involve all sites including the MSG. Dr. McDermott, from Rochester, will be the HNC Biostatistician. The Charcot Marie Tooth Association (CMTA), CMT United Kingdom (CMTUK) and TREAT-NMD organizations will interact extensively with the HNC.

Public Health Relevance

These projects will provide insights into disease mechanisms develop therapies and educate future investigators for the inherited neuropathies.

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 (ZRG1-HOP-Y (50))
Program Officer
Porter, John D
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Wayne State University
Schools of Medicine
United States
Zip Code
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, ├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

Showing the most recent 10 out of 189 publications