Abstract

STANDARD OF CARE CMT1, CMT2 and CMT4 are caused by mutations in > 80 genes. Despite the genetic heterogeneity there are clinical similarities in most patients, even if the speed of progression may vary. Distal wasting, weakness and sensory loss that begin in the lower limbs and progress proximally in a length-dependent manner characterize most forms of CMT. Despite progress in identifying its causes there are still no published comprehensive standards of care (SOC) for CMT. We have a unique opportunity to develop them. During the initial cycle of our RDCRC, we have enrolled over 6500 patients into the protocols of the INC. We have performed preliminary studies on the usage of next generation sequencing (NGS), the benefits of aerobic exercise and the approaches to orthopedic surgery in patients with CMT. All three of these areas are important to patients with CMT and all three lack SOC. In the upcoming cycle we propose the following three Specific Aims:
Aim 1 : Develop genetic diagnostic guidelines for CMT based on NGS technology.
Aim 2 : Develop evidence-based guidelines for the use of aerobic exercise in CMT.
Aim 3 : Convene an international workshop to develop SOC for CMT and to identify areas of SOC that need further study to develop evidence based guidelines.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54NS065712-10
Application #
9344693
Study Section
Special Emphasis Panel (ZNS1)
Project Start
Project End
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
10
Fiscal Year
2017
Total Cost
Indirect Cost

  Institution

Name
University of Iowa
Department
Type
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242

  Publications

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
Saghira, Cima; Bis, Dana M; Stanek, David et al. (2018) Variant pathogenicity evaluation in the community-driven Inherited Neuropathy Variant Browser. Hum Mutat 39:635-642
Shy, Michael; Rebelo, Adriana P; Feely, Shawna Me et al. (2018) Mutations in BAG3 cause adult-onset Charcot-Marie-Tooth disease. J Neurol Neurosurg Psychiatry 89:313-315
Laurá, Matilde; Singh, Dishan; Ramdharry, Gita et al. (2018) Prevalence and orthopedic management of foot and ankle deformities in Charcot-Marie-Tooth disease. Muscle Nerve 57:255-259
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

Showing the most recent 10 out of 189 publications