According to an article from Charcot-Marie-Tooth News, a study was conducted that discovered three new mutations on the GJB1 gene that result in X-linked Charcot-Marie-Tooth disease (CMTX1). The study, which was published in Frontiers of Neurology, suggests that genetic testing for CMT should now cover these regions of the GJB1 gene as well.
About Charcot-Marie-Tooth Disease
Charcot-Marie-Tooth (CMT) disease, also known as hereditary motor and sensory neuropathy, is a neurological disorder that affects the peripheral nervous system. It occurs as the result of mutations in various genes (CMT1, CMT2, CMT3), all of which result in the death of peripheral nerves. Depending on which gene is affected, this condition can be inherited in an autosomal dominant or recessive pattern. There is also an X-linked version of the disease, which is passed down through mutations of the GJB1 gene. Regardless of inheritance, affected individuals may experience foot deformities, difficulty with walking and fine motor skills, weakness in the hands and feet, and lower leg deformities. There is currently no cure for this disease, although physical and occupational therapy are used to maintain muscle strength and use. Pain medications may also be prescribed.
About the Mutations
Three new mutations have been found on the GJB1 gene, adding to the 450 alterations that have already been discovered. These changes are all in the coding regions of the gene, meaning that they play a role in producing the connexin-32 protein.
This protein is found in Schwann cells and oligodendrocytes, both of which are responsible for creating the myelin sheath that protects nerve cells. Without the myelin sheath, there will be no proper transmission within the nervous system. This means that when the GJB1 gene is mutated, the nerve cells cannot communicate properly, which then leads to the characteristic symptoms of CMT.
Chinese researchers wanted to better understand these mutations, so they examined the genomes and clinical characteristics of 580 people with CMTX1 along with 650 healthy people to act as a control group. Using genetic sequencing methods, the researchers found 86 participants with CMTX1 with 34 different mutations among them. Within these mutations, three were undiscovered.
Those who had the new mutations all presented similarly: muscle weakness, juvenile-onset, slower nerve conduction velocities, and lower tendon reflexes. The only difference was the females had less severe symptoms with a later onset. As the GJB1 gene is on the X chromosome, this makes sense.
Five other mutations were discovered as well, all of which were associated with specific symptoms, such as vertigo, lack of muscle coordination, weakness on only one side of the body, inability to form words, and difficulty speaking.
These findings expand the knowledge of CMTX1, which could lead to better diagnostics and treatments. Hopefully there will be further research into these mutations.
