Genetics may play a larger role in causing amyotrophic lateral sclerosis — Lou Gehrig’s disease — than previously believed, potentially accounting for more than a third of cases, researchers at Cedars-Sinai Medical Center announced Friday.
The study by investigators at Cedars-Sinai and Washington University in St. Louis also showed that patients with defects in two or more ALS-associated genes experience disease onset about 10 years earlier than patients with single- gene mutations.
The findings, published online in Annals of Neurology, shed light on the genetic origins of ALS, especially in patients who had no prior family history of the disease, said Dr. Robert H. Baloh, director of neuromuscular medicine in the Department of Neurology and director of the ALS Program at Cedars-Sinai.
Typically, researchers classify 90 percent of ALS cases as sporadic, meaning they occur in patients without a family history of the disease.
In their study, however, the researchers found a significant degree of genetic involvement in patients with no family history.
Examining DNA from 391 individuals, they identified numerous new or very rare ALS gene mutations in such people. Added to the 10 percent of cases already known to be genetic because of family history, the study suggested that more than one-third of all ALS could be genetic in origin.
Baloh, the senior author of the study, said the presence of the new and rare mutations, found among 17 genes already known to be associated with ALS, does not necessarily mean they all cause the disease.
But they are considered likely suspects especially in combination. ALS often is caused by well-known defects in single genes, but recent studies have suggested that some cases could be brought on by the simultaneous occurrence of two or more lesser genetic defects. In theory, each mutation alone might be tolerated without initiating disease, but in combination they exceed the threshold required for disease development.
— City News Service