Delineating the genetic heterogeneity of ALS using targeted high-throughput sequencing

Mutations in at least 17 different genes can cause amyotrophic lateral sclerosis (ALS), and mutations in a further 16 are likely to increase susceptibility.  In the most extensive study of its kind, we used modern DNA sequencing to characterize the relative contributions of these 33 disease genes to the risk of developing ALS in Ireland. We found that at least  17% of people with ALS carried mutations that might be disease causing, and that  9.7% carried mutations that have been previously established as causative . We also found that multiple mutations can occur in the same individual and may be required to trigger disease onset. Finally, we found that the spectrum of disease mutations among Irish patients differed significantly from that reported across other European populations, suggesting that some forms of ALS may be population specific. (By Kevin Kenna, http://jmg.bmj.com/content/early/2013/07/23/jmedgenet-2013-101795 )