Genetic clues to basis of ALS

11 May 2010

A pair of studies from the University of Sheffield have revealed genetic clues to the basis of amyotrophic lateral sclerosis (ALS), the neurodegenerative disease that affects physicist Stephen Hawking.

Approximately 5 per cent of ALS cases are inherited; previous studies have linked mutations in the gene FUS/TLS to the disorder. Professor Pamela Shaw and colleagues at Sheffield investigated the frequency of these mutations in a cohort of people with ALS from the North of England, finding mutations in 5 per cent of inherited ALS cases.

In a separate study, the team looked at mutations in the gene CHMP2B, associated with frontotemporal dementia, which occurs in 3-10 per cent of people with ALS. Again looking at a group of patients from the North of England, their analysis found CHMP2B mutations in around 1 per cent of ALS cases. That figure rose to 10 per cent for those with ALS affecting mainly the lower motor neurons in their brainstem and spinal cord (ALS commonly causes injury and death to both lower motor neurons in these sites and to upper motor neurons within the motor cortex of the brain). Further evidence tracking multiple affected individuals in a family is needed to confirm the link, the researchers say.

"Accurate classification of ALS is really important to identify the best protective strategies and to optimally design human clinical trials," said Professor Shaw. "The discovery of two new genes is a step forward in classification and opens up new approaches to understanding the biological mechanisms underlying this devastating disease."

Image: Motor neurons. Credit: Dr David Becker

References

Hewitt C et al. Novel FUS/TLS mutations and pathology in familial and sporadic amyotrophic lateral sclerosis. Arch Neurol 2010;67(4):455-61.
Cox LE et al. Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS). PLoS ONE 2010;5(3):e9872.