Researchers have Uncovered a New Mitochondrial Gene Mutation Related to Charcot-Marie-Tooth Disease

In a recent study, researchers have uncovered a second gene located within the mitochondria that is associated with Charcot-Marie-Tooth Disease (CMT). This study was recently published in Annals of Neurology.


Over 100 different  genes are documented to be associated with the development of CMT. All of these genes code for a specific protein, and most of these genes have been found within the DNA. Specifically, they have been located within the nucleus of the cell.

One gene located within the mitochondria was also previously found to cause CMT.

This latest discovery of this second gene demonstrates the diversity of the genetic causes of CMT, especially because this new gene does not code for the protein that all of the other genes leading to CMT do.

The Study

This study took place in Venezuela. A large family indigenous to Venezuela was found to have around 100 individuals out of the 3,700 living with symptoms similar to that of CMT.

Specifically, 97 individuals expressed symptoms. 55 of these were female and 42 were male. All patients were diagnosed with either nerve disease or clinical neuropathy. In every case, the individuals affected had inherited the disease from their maternal side. This is consistent with previous findings.

The research team was able to assess 44 of the individuals who presented with symptoms. Of these, there was an average age of 41.1. Clinical symptoms ranged in onset from 1 to 68 with an average of 15.3. Symptoms of these patients included-

  • Muscle weakness
  • Muscle wasting
  • Loss of muscle coordination
  • Difficulty in mobility
    • 31 were able to walk
    • 6 used a cane
    • 2 used a walker
    • 5 required a wheelchair
  • 22 had gate impairment
    • 18 of these had axonal damage in their motor and sensory neurons    

Many of those with the axonal form of CMT don’t have a clear genetic diagnosis. This form leads to the degeneration of the peripheral nerve axons. These connect the brain as well as the spinal cord to the rest of the body.

The researchers then conducted DNA sequencing of the mitochondrial in 3 of the individuals as well as one of the family members who was an asymptomatic carrier.

They found the mutating gene was mt-tRNAVal(MT-TV). This gene is responsible for coding for tRNA. tRNA works to carry amino acids to proteins. They also found unrelated gene mutations in the individuals living with symptoms. However, the asymptomatic carrier did not present with any of these other gene mutations.

The research team also did an analysis of the muscle tissue and nerve biopsies from these individuals. They found-

  • Muscle denervation
  • Muscle reinnervation
    • Greater effect in more severely impacted individuals
  • Mitochondrial abnormalities
  • Lower activity in the mitochondrial proteins responsible for producing energy
    • Greater effect in the more severely impacted individuals
  • Reduction in MT-TV levels
    • Greater effect in the more severely impacted individuals

Looking Forward

The researches emphasize that their findings demonstrate the need for mtDNA sequencing for CMT patients who do not yet have a genetic diagnosis. This kind of testing could be beneficial even if other features of mitochondrial disease aren’t present.

The team also want to continue their study to find the exact method that this mutated gene leads to CMT.

This study did have limitations which are important to note. Specifically, there is the potential for the neuropathy to have been caused by another condition. Additionally, analysis was difficult due to limited access to tissue samples and genetic records from families.

You can read more about this study here.

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