Researchers have known, for a while, that a variety of gene mutations contribute to different subtypes of Charcot-Marie-Tooth disease. The specific condition is dependent on which gene is mutated. But according to Charcot-Marie-Tooth News, scientists recently linked DST gene mutations to Charcot-Marie-Tooth disease type 2 (CMT2). Prior to these findings, this genetic mutation has never before been linked to this condition. Read the full findings in Neurology Genetics.

Gene Mutations

Over 80 different gene mutations cause CMT subtypes. However, it is important to research these varied mutations. By better understanding what occurs with each mutation, scientists may better treat patients with CMT.

In this case, researchers discovered the link to DST gene mutations through a familial study. At 13, the older sister began having trouble walking. By 29, she was diagnosed with CMT2; by 55, she used a walker. Her younger brother received a CMT2 diagnosis when he was 18. CMT2 is characterized by affected axons, a type of nerve fiber.

Researchers began examining their condition through whole-exome sequencing (WES). This sequences under 2% of the genome to search for proteins and biomarkers of CMT. For a more comprehensive understanding, both siblings, as well as an unaffected sibling, underwent WES.

Through this, researchers discovered the DST mutations. One DST gene from each parent had a unique mutation. As a result, the siblings, who had both gene mutations, spurred CMT development. The mutations prevented DST from producing bullies pemphigoid antigen 1 (BPAG1). This inhibition is linked to axonal nerve damage.

Moving forward, researchers hope to leverage this knowledge for continued CMT treatment development.

Charcot-Marie-Tooth Disease

Sometimes referred to as hereditary motor and sensory neuropathy, Charcot-Marie-Tooth disease (CMT) is a genetic neurological disorder. CMT impacts the peripheral nerves, or the 43 pairs of motor and sensory nerves near your brain and spinal cord. It is caused by a variety of gene mutations which prevent communication between muscles and peripheral nerves. Generally, patients inherit CMT. However, in rare cases, gene mutations arise spontaneously.

Symptom onset often occurs in adolescence or early adulthood. Symptoms include:

• High arches, hammertoes, or other foot deformities
• Slow reflexes
• Foot drop
• Muscle weakness in the lower extremities
• “Pins and needles” sensation
• Difficulty with walking
• Loss of fine motor skills
• Muscle atrophy in the hands
• Rhythmic muscle contractions throughout the body

Learn more about CMT.