Symptoms and genetic basis:
Charcot-Marie-Tooth disease (CMT) is the most commonly inherited peripheral neuropathy with a prevalence of 1 in 2500 births. It is characterized by a progressive deterioration of peripheral nerves (nerves that are not a part of the central nervous system) and the consequent wasting away of muscles at the ends of arms and legs.
The most common subtype of CMT is called CMT1A, which starts in the second or third decade of life, and which has symptoms ranging from mild loss of motor and sensory function to severe hand and foot deformities. CMT1A is caused by a duplication of the region of chromosome 17 that contains a gene called PMP22. This gene duplication results in overproduction of the corresponding protein product.
Further understanding of the disease
There are several approaches being taken at Baylor College of Medicine (BCM) to develop a more comprehensive understanding of peripheral nerve biology and the disturbances that cause Charcot-Marie-Tooth disease and related disorders. These approaches include the study of genes known to be involved and searches for others, genetic comparisons between humans and other species, and investigation of genetic mutations that occur in Charcot-Marie-Tooth disease patients.
In particular, researchers will test the following hypotheses: (1) that identifying genes involved in inherited neuropathies will provide information regarding peripheral nerve development, structure and function; (2) that genes interacting with a protein called EGR2 (known to be involved in peripheral nerve gene expression) may be involved in peripheral neuropathies; and (3) that certain DNA (deoxyribonucleic acid) structures may be particularly susceptible to rearrangements that lead to disease (like the duplication that causes CMT1A).
Work towards therapy
It is apparently very important that expression of the PMP22 gene be within certain rather narrow limits, since overexpression produces CMT1A and underexpression results in a different peripheral neuropathy. Any therapeutic measure aimed at correcting either of these disorders by altering PMP22 expression must therefore be carefully controlled to avoid causing the other disorder. Researchers at BCM are investigating proteins and DNA sequences that are involved in controlling the level of expression of the PMP22 gene. Better understanding of how this gene is controlled may provide information and tools for future treatment options.
- Charcot-Marie-Tooth Association
- Muscular Dystrophy Association
- National Ataxia Foundation
- National Institute of Neurological Disorders and Stroke
- National Organization for Rare Disorders
- Neuropathy Association