Genetics May Play Bigger Role in Amyotrophic Lateral Sclerosis

the Neurology Advisor take:

Genetics may account for up to one-third of amyotrophic lateral sclerosis (ALS) cases, a fraction that is larger than previously thought, according to a study published in the Annals of Neurology.

Previously, it had been estimated that up to 90% of ALS cases occur sporadically, without any genetic link. However, this new study challenges that number.

The study included 391 patients with ALS from the United States. The researchers used new techniques, called pooled DNA sequencing, to sequence 17 genes that are linked to ALS in each participant.

In these 17 genes, the researchers found 27 novel mutations as well as 38 others that are very rare among control populations. The variations were found in 64.3% of participants with a known family history of ALS and in 27.8% sporadic patients. The latter rate is significantly higher than rates found in other studies that used less compressive sequencing approaches.

The researchers also found that in the 3.8% of participants who had more than one ALS gene, disease onset was 10 years earlier compared with those with only one gene. In most of these cases, one mutation was a known ALS marker and the other had unknown significance.

The researchers hope that these results will help pinpoint genes to target for gene-specific therapies to correct these defects.