Genetic Mutation May Cause Peripheral Neuropathy

Chicago, December 28, 2007: In a report submitted to the Journal of Neuroscience this week, researchers at the University of Chicago have identified an inherited genetic mutation that may cause a human nerve disorder called peripheral neuropathy (PN). PN affects about 3% of individuals over the age of 60, and includes symptoms such as pain in the limbs, hands, and feet, as well as increasing weakness and numbness in the extremities. Symptoms become progressively worse over time, due to increased damage to nerves located outside the central nervous system (brain and spinal cord). Currently, there is no known treatment.

Brian Popko and his colleagues recently discovered that mice carrying mutations in only one copy of a gene coding for part of the dynein protein ended up having severe problems with proprioception, which is the ability to perceive the spatial orientation of body parts. Dynein is essential for the proper function of sensory nerve cells. Found throughout the body, the protein plays an important role in axon to cell body signaling. Axons are the elongated tendrils of nerve cells that relay chemical messages, and which are the main means of nervous communication.

Mice with the dynein protein mutation also had hind leg movement problems, something that is commonly evidenced in many human neuropathies as well, especially Charcot-Marie-Tooth (CMT) Disease and hereditary sensory neuropathy. CMT Disease affects about 1 in 2,500 individuals and results in progressive loss of muscle tissue as well as loss of sensation in limbs. Damage to both sensory and motor nerves is highly characteristic of this disease. Hereditary sensory neuropathy results in damage to the sensory nerves only, resulting in loss of limb sensation and reflex.

The importance of dynein cannot be understated: mice containing mutations in both copies of the dynein gene die before birth. Furthermore, mutations in different parts of the dynein gene produced different variations of neuropathy.