Genetic mutations may cause more cases of amyotrophic lateral sclerosis (ALS) than scientists previously had realized, according to researchers at Washington University School of Medicine in St. Louis and Cedars-Sinai Medical Center in Los Angeles. The scientists also showed that the number of mutated genes influences the age when the fatal paralyzing disorder first appears. The study appears online in Annals of Neurology.
Scientists have linked mutations in more than 30 genes to ALS. Alone or in combination, mutations in these genes can cause the disease in family members who inherit them. Roughly 90 percent of patients with ALS have no family history of the disease, and their condition is referred to as sporadic ALS. Scientists had thought mutations contributed to barely more than one in every 10 cases of sporadic ALS. But researchers recently started to suspect that patients with sporadic ALS carry mutations in the 30 genes linked to ALS more often than previously thought. The new study is among the first to prove this suspicion correct.
“To our surprise, we found that 26 percent of sporadic ALS patients had potential mutations in one of the known ALS genes we analyzed,” says co-senior author Matthew Harms, MD. “This suggests that mutations may be contributing to significantly more ALS cases.”
The scientists used a sequencing technique devised at Washington University to look at 17 known ALS genes in the DNA of 391 patients with ALS. Like the overall ALS patient population, 90 percent of the patients had no family history of disease.
The study also shows that having mutations in more than one ALS gene can accelerate the onset of symptoms. In patients with only one mutation, the average age of onset was 61, but in those with more than one mutation, the average age of onset was 51. The scientists are analyzing genetic data from additional patients with ALS to confirm their findings.
Read the study abstract in Annals of Neurology
