Scientists have revealed a new genetic cause of Charcot-Marie-Tooth disease (CMT), an inherited neurological disorder. New research has identified mutations in the gene PMP2 as another cause of CMT type 1 – the disease’s most common form. This breakthrough is the result of an international academic collaboration, including VIB, the University of Antwerp, the University of Pennsylvania, the University of Miami and the Medical University of Innsbruck. The study was published in the March issue of the leading neurology journal Brain.

Charcot–Marie–Tooth disease affects approximately 1 in 2,500 people. Currently incurable, this disorder of the peripheral nervous system is characterized by the progressive loss of muscle tissue, as well as numbness and weakness in the hands and feet. CMT1, the most common category, is caused by a malfunction in cells that make up the myelin sheath, the protective coating that enwraps nerve fibers and allows them to conduct nerve signals at high speed.

CMT family research

The study was launched at the University of Pennsylvania, where neurologists studied a father and son with CMT1. Because none of the known CMT1-causing genes were affected in either subject, the scientists used advanced sequencing technology to search for new genetic causes of the disease. They discovered a new mutation in PMP2, a gene that encodes a protein crucial to the human peripheral nervous system. As the affected father and son were the only family members to carry this mutation, these findings were a strong indication that PMP2 mutation causes CMT1. To confirm this hypothesis, the scientists reached out to other renowned CMT researchers around the globe.

Albena Jordanova (VIB-University of Antwerp): “Because the Pennsylvania researchers needed an independent finding of mutation in the same gene in a non-related CMT family, they decided to call on VIB’s profound CMT expertise. In our lab, we screened an additional 136 European families with CMT1 for mutations in PMP2, after which we identified one Austrian family with several affected members who share a different mutation in PMP2. In this way, we provided another proof of the identification of a novel CMT1-causing gene.”

New step toward curing CMT

The joint collaboration expanded the number of genes known to cause CMT1. In addition to the knowledge gathered about the mutations itself, the study’s research process and methodology will help neurologists follow similar scientific avenues to better understand the disease’s ins and outs – and, in time, to find a cure. Meanwhile, the study paved the way for a highly-acclaimed paper recently published in the British scientific neurology journal Brain.

​De novo PMP2 mutations in families with type 1 Charcot-Marie-Tooth disease, Motley et al., Brain 2016

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