Study Identifies Mutations in Charcot-Marie-Tooth Disease that Worsen Peripheral Nerve Damage

Study Identifies Mutations in Charcot-Marie-Tooth Disease that Worsen Peripheral Nerve Damage

By Staff

Recently, a press release was sent out by Jackson Laboratories regarding the identification of “specific genetic mutations in Charcot-Marie-Tooth (CMT) disease that worsens peripheral nerve damage.”

Named after the researches who discovered it (and having nothing to do with teeth), Charcot-Marie-Tooth disease (CMT) “is one of the most common inherited neurological disorders, affecting approximately 1 in 2,500 people in the United States.”, according the National Institute of Neurological Disease and Stroke. “CMT, also known as hereditary motor and sensory neuropathy (HMSN) or peroneal muscular atrophy, comprises a group of disorders that affect peripheral nerves.”

Although not considered fatal, CMT affects motor and sensory nerves, and causes mild to severe pain. CMT commonly results in weakness and muscle atrophy of the feet, lower legs, and eventually the hands, requiring some people to rely on foot or leg braces or other orthopedic devices to maintain mobility.

While the research was performed using mouse models of CMT, the study may lead “to better diagnostics for CMT and also suggests potential treatment strategies” for CMT and other peripheral neuropathies.

Click here to learn more about Charcot-Marie-Tooth (CMT) disease.

The press release:

JAX researchers identify mutations in Charcot-Marie-Tooth disease that worsen peripheral nerve damage
A combination of specific genetic mutations in Charcot-Marie-Tooth (CMT) disease that worsens peripheral nerve damage could be a helpful biomarker for predicting the severity of a given case of CMT, a Jackson Laboratory research team reports.

Hereditary neuropathies are neurological disorders that cause damage to the peripheral nerves, the bundles of nerve cell fibers that connect the brain and spinal cord to muscles and sensory organs. The disease known as CMT is actually a category of inherited neuropathies, involving more than 80 different genetic mutations with varying impact on the severity of symptoms, which include sensory deficits and muscle atrophy.

Peripheral nodes are gaps in the myelin sheaths that cover axons, long projections of nerve cells. These exposed gaps are highly active interchanges, with sodium channels where ions get exchanged to activate nerves. The research team, led by JAX Professor Robert Burgess, Ph.D., looked at peripheral nodes known as the nodes of Ranvier in mouse models of CMT.

Either of two mutations impacting Scn8a — a sodium channel that is vital to the proper conduction of nerve impulses at the nodes of Ranvier — caused decreased sodium currents that led to severe neurological problems in the CMT mice, Burgess says. “These mutations, while innocuous on their own, can synergize with CMT-associated mutations to cause much more severe disease.”

The study, published in Cell Reports, provides a path to better diagnostics for CMT and also suggests potential treatment strategies: counteracting the decreased sodium currents by increasing sodium currents or reducing potassium currents.

In addition to conducting CMT research, Burgess is a principal investigator of the JAX Resource for Research of Peripheral Neuropathy to accelerate the creation, distribution and use of high-priority mouse models for CMT research.


Morelli et al.: Severity of demyelinating and axonal neuropathy mouse models is modified by genes affecting structure and function of peripheral nodes. Cell Reports, March 28, 2017, http://dx.doi.org/10.1016/j.celrep.2017.03.009.

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Authored by: Staff