The researchers discovered that people who inherit two faulty copies of a gene called ARHGAP19 – one copy from each parent – develop CMT.

The finding means that people with two faulty copies of the gene may now be able to receive a definitive genetic diagnosis. It could also help families better understand the cause of their condition and the potential risk for future children. It may also help guide the development of targeted therapies.

The research team used a combination of laboratory experiments, including studies of cells from patients with CMT, alongside computer-based analysis.

Their work showed that mutations in the gene stop ARHGAP19 from carrying out its normal role in motor neurons – the nerve cells that control muscles.

The research led by Dr Natalia Dominik, NIHR BRC Translational Neuroscience Research Fellow, is already using this discovery to investigate whether existing medicines could help people with ARHGAP19 linked CMT.

In addition, the next stage of the research will focus on understanding exactly how mutations in ARHGAP19 lead to nerve damage and whether other cell types also play a role in the disease.

The team will also explore whether the discovery could help improve understanding of other related inherited conditions.

Charcot-Marie-Tooth disease and related conditions are among the most common inherited neuromuscular disorders, yet around 1 in 4 patients do not receive a clear genetic diagnosis.

Dr Dominik, based at the Department of Neuromuscular Disorders within the UCL Queen Square Institute of Neurology, said: “Ultimately we want to find new and better therapies for patients, and the discovery we made is one step along the way to doing this.”

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