Newly Discovered Gene Mutation Linked to Nerve Diseases

Dec 28, 2009 By Marla Paul

(PhysOrg.com) -- Researchers from the Northwestern University Feinberg School of Medicine have identified mutations in the gene for TRPV4 that cause two related degenerative motor nerve disorders, scapuloperoneal spinal muscular atrophy (SPSMA) and hereditary motor and sensory neuropathy type IIC (CMT2C).

These disorders cause progressive weakness of the limbs, breathing muscles and vocal cords. The Northwestern University researchers also established that TRPV4 is involved in homeostasis of intracellular calcium during axonal activity. As a result, this discovery has wider implications for understanding non-genetic neuropathies and motor axon degeneration.

Han-Xiang Deng, MD, Ph.D., associate professor of neurology, and Teepu Siddique, MD, the Les Turner ALS Foundation/Herbert C. Wenske Professor, both of the Davee Department of Neurology and Clinical Neurosciences and their colleagues published these findings in the online edition of Dec. 27. Dr. Siddique is also a neurologist at Northwestern Memorial Hospital.

"Abnormally functioning TRPV4 receptors may drive excess calcium into neuronal extensions called axons," said Siddique, who is also director of the Division of Neuromuscular Medicine at Northwestern's Feinberg School of Medicine. "We think this may be a mechanism by which axons of motor or may be damaged in a variety of neurological conditions."

The discovery adds a new dimension to scientists' understanding of the way innervate muscle function. "We know an electrical impulse starts from the spinal cord and goes out to the muscle," Deng said. "That is how things have been understood. Now we have this receptor that may modulate axonal activity, so, if it is not functioning properly, there may be nerve damage."

Sididque noted that because TRPV4 receptors are activated by pressure, amongst other modalities, their malfunctioning could also be relevant to compression . He further said the role of TPRV4 in the pathophysiology of other spinal muscular atrophies and amyotrophic lateral sclerosis (ALS, also called Lou Gehrig disease) should also be investigated. ALS is a progressive and usually fatal neurodegenerative disease that affects nerve cells in the brain and spinal cord.

Robert Delong, MD, now professor emeritus of pediatrics at Duke University School of Medicine, and Siddique, first identified scapuloperoneal in a large New England family of French-Canadian origin in 1992. In 1994, Peter Dyck, MD, professor of neurology at the Mayo Clinic, identified the related disorder hereditary motor and sensory neuropathy type IIC in an American family of English and Scottish descent. In this new study, gene mapping and sequencing of DNA from these two families revealed the key TRPV4 gene mutations.

Explore further: Could ibuprofen be an anti-aging medicine? Popular over-the counter drug extends lifespan in yeast, worms and flies

add to favorites email to friend print save as pdf

Related Stories

Mutation may cause inherited neuropathy

Dec 26, 2007

Mutations in a protein called dynein, required for the proper functioning of sensory nerve cells, can cause defects in mice that may provide crucial clues leading to better treatments for a human nerve disorder known as peripheral ...

Researchers gain new insights on spinal muscular atrophy

May 29, 2008

Researchers from the University of Pennsylvania School of Medicine discovered that the effect of a protein deficiency, which is the basis of the neuromuscular disease spinal muscular atrophy (SMA), is not restricted to motor ...

Motor neuron disease and toxic substances: Possible link?

Mar 20, 2008

Motor neuron disease is a rare, devastating illness in which nerve cells that carry brain signals to muscles gradually deteriorate. One form of it, Lou Gehrig’s disease or ALS (amyotrophic lateral sclerosis), is familiar ...

Promising new nanotechnology for spinal cord injury

Apr 02, 2008

A spinal cord injury often leads to permanent paralysis and loss of sensation below the site of the injury because the damaged nerve fibers can't regenerate. The nerve fibers or axons have the capacity to grow again, but ...

Recommended for you

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.