Spinal Muscular Atrophy Gene Mutation Identified

Scientists at Cedars-Sinai Medical Center have uncovered a gene mutation responsible for spinal muscular atrophy with lower extremity predominance (SMA-LED)—a rare, inherited disease that causes progressive muscle degeneration and weakness.

“Typical spinal muscular atrophies begin in infancy or early childhood and are fatal, involving all motor neurons, but SMA-LED predominantly affects nerve cells controlling muscles of the legs. It is not fatal and the prognosis is good, although patients usually are moderately disabled and require assistive devices such as bracing and wheelchairs throughout their lives,” said Dr. Robert Baloh, director of Cedars-Sinai Medical Center’s neuromuscular division and study author.

Baloh and researchers with the neuromuscular division found that a mutation known as DYNC1H1 disrupts the function of a molecule inside cells that acts as a motor to transport cellular components. Some subjects with these mutations had global developmental delays plus weakness, indicating brain involvement.

“Our observations suggest that a range of DYNC1H1-related disease exists in humans—from a widespread neurodevelopmental abnormality of the central nervous system to more selective involvement of certain motor neurons, which manifests as spinal muscular atrophy,” Baloh said.

Although the mutation is responsible for some inherited cases of SMA-LED, the genetic mutation is absent in others.

The researchers hope the findings will shed light on the common form of SMA and amyotrophic lateral sclerosis or ALS.

The study was published in the March issue of Neurology.