# Genomic Studies in Charcot-Marie-Tooth Disease

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2021 · $629,933

## Abstract

PROJECT SUMMARY
The various forms of Charcot-Marie-Tooth disease (CMT) comprise a genetically heterogeneous set of
peripheral neuropathies. Currently >90 different CMT genes have been identified; yet, for the axonal CMT2
subtype these genes explain only 30-40% of the genetic effect. Especially the application of exome sequencing
has led to an unprecedented pace in identifying about half of those genes in the past five years. We have been
at the forefront of this development with 22+ published new gene identifications in the past seven years. This
success was only possible through broad national and international collaborations, data sharing, and the
development of advanced analysis tools and methods. We also learned that despite exome sequencing, over
50% of axonal CMT patients remain undiagnosed pointing towards even more genes; however, our preliminary
data also support the existence of non- coding variation as Mendelian allele contributor. In this grant we will
continue our highly impactful work in CMT family recruitment, exome sequencing and traditional gene
identification. In addition, we will expand the genetic studies to whole genome sequencing with a focus on
families already explored unsuccessfully in whole exome studies. We further plan to perform the first large rare
variant burden analysis in the rare disorder CMT2 – this is only possibly through the exceptional clinical
resources we have built over the past decade. Finally, with many CMT genes available, we will perform
statistical network analyses on a CMT-ome to identify gene modules and pathways that will be the starting
point of polypharmacology and provide insight into pathophysiology of peripheral nerve degeneration. All data
will be available in real-time to an existing network of CMT investigators worldwide, and deposited in dbGAP
annually.
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## Key facts

- **NIH application ID:** 10226201
- **Project number:** 5R01NS105755-03
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** MICHAEL E. SHY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $629,933
- **Award type:** 5
- **Project period:** 2019-09-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10226201

## Citation

> US National Institutes of Health, RePORTER application 10226201, Genomic Studies in Charcot-Marie-Tooth Disease (5R01NS105755-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10226201. Licensed CC0.

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