Discovery of a new gene found to cause CMT2

Two CMT Research Foundation Scientific Advisory Board members make a new discovery

Congratulations to our Scientific Advisory Board members Drs. Charlotte Sumner and William Motley on their recent publication identifying a new gene implicated in CMT2.    Genetic analyses were performed on patients in two unrelated families with CMT2 involving mild limb weakness and nerve damage of the vocal cords.

Two different gene mutations in the JAG1 gene were identified that were predicted to decrease the function of this key member of the  Notch signaling pathway, which plays a critical role in development.  Further experiments in cultured cells showed that these mutations led to decreased expression of JAG1.  Creation of a mouse model expressing one of the human JAG1 mutations resulted in peripheral nerve disease “highlighting a critical role for JAG1 in maintaining peripheral nerve integrity”.

Given that therapies inhibiting JAG1 are currently in development for cancer, these studies raise caution that peripheral neuropathy may be an associated side effect and should be evaluated in clinical trials.