Researchers at China’s Shandong University have discovered a novel gene mutation in a Chinese family with Charcot-Marie-Tooth (CMT) disease type 2.
Their study, “A novel mutation of LRSAM1 in a Chinese family with Charcot-Marie-Tooth disease,” appeared in the Journal of the Peripheral Nervous System.
CMT, one of the most common hereditary neurological disorders, is a nerve disease that primarily damages arms and legs. Its two forms are type 1, which is caused by loss of myelin sheath — the protective layer that enables effective neuronal communication — and the less common type 2, which results from direct damage to the nerve axon.
Mutations in at least 80 genes have been linked to CMT. One of these is in the LRSAM1 gene, which causes the relatively mild and benign CMT type 2P. Patients with this type of CMTD typically present symptom onset between 20 and 40 years of age.
The LRSAM1 protein belongs to a group of enzymes called RING-finger E3 ubiquitin ligase, which are produced in the fetal and adult spinal cord, sensory neurons and all developing muscles.
Research suggests that the LRSAM1 protein may play a neuroprotective role in Huntington’s disease, potentially delaying disease onset, slowing its progression and prolonging patients’ lifespan.
The study characterizes a novel mutation in the LRSAM1 gene, in a three-generation family with autosomal dominant CMT type 2. This means that the mutated gene is located in a non-sex chromosome and only one copy of the gene is required to get the disease.
Standard motor and sensory nerve conduction tests were performed in all available family members. The genetic analysis showed that the mutation was present in six patients, two of them deceased. The four living patients were all males (mean age 42 years), who had initial difficulty in walking caused by slowly progressive weakness of the lower limbs. The initial duration of CMT in these patients was about 10 years, with a late onset.
Scientists also observed reduced or absent tendon reflexes, and mild sensory loss, numbness and tingling in the feet of all four subjects. One patient showed atrophy in the distal parts of the lower limbs. Another patient required a walking stick seven years after disease onset.
Motor and sensory studies revealed mild to moderate reduction in nerve conduction velocity, mainly in the lower limbs.
“Clinical and electrophysiological features of all patients are typical of [CMT] type 2, including distal weakness beginning in the lower limbs, depressed or absent tendon reflexes and mild sensory disturbance,” researchers wrote, adding that further studies are needed to explain how each mutation in the LRSAM1 gene causes CMT.