The underlying defect in CMT is muscle atrophy due to a lack of stimulation from the nerves. That lack of stimulation stems from one of two underlying causes, which define the two primary forms of the disease: CMT type 1 and 2.
In CMT type 1, the speed of the nerve impulse slows due to degradation of the protective myelin sheath that normally covers nerve axons, Zchner explained. Axons are the cable-like extension of the neuron from the cell body in the spinal cord to the juncture, or synapse, between the nerve ending and muscle. Demyelinated axons conduct nerve impulses at slower rates than normal, causing communication to stall.
In contrast, patients with CMT type 2, which results from a breakdown in the nerve axon itself, exhibit normal, or near normal, nerve impulse speeds. Defects in multiple genes have been found to underlie CMT types 1 and 2.
In rare cases, family members exhibit a form of the disease with symptoms that fall somewhere between those normally associated with either CMT type 1 or 2, Zchner said. Earlier research had linked this "intermediate" form of the disease to unknown genetic defects at three different chromosomal locations.
To further narrow the search for causes, the Duke team screened three unrelated families, with intermediate CMT linked to one of those chromosomal regions, for defects in candidate disease genes. Family members who had the condition all exhibited unique mutations in the well-studied dynamin 2 gene, they found.
The protein encoded by dynamin 2 modulates several critical cellular processes, which might explain its effects on the nervous system in people with CMT, Vance said. For example, the protein plays an important role in the recycling of chemical nerve messengers, or neurotransmitters, in nerves of the peripheral nerv
'"/>
Contact: Kendall Morgan
kendall.morgan@duke.edu
919-660-1306
Duke University Medical Center
31-Jan-2005