Novel genes associated with amyotrophic lateral sclerosis: diagnostic and clinical implications

Publication date: Available online 16 November 2017 Source:The Lancet Neurology Author(s): Ruth Chia, Adriano Chiò, Bryan J Traynor Background The disease course of amyotrophic lateral sclerosis (ALS) is rapid and, because its pathophysiology is unclear, few effective treatments are available. Genetic research aims to understand the underlying mechanisms of ALS and identify potential therapeutic targets. The first gene associated with ALS was SOD1, identified in 1993 and, by early 2014, more than 20 genes had been identified as causative of, or highly associated with, ALS. These genetic discoveries have identified key disease pathways that are therapeutically testable and could potentially lead to the development of better treatments for people with ALS. Recent developments Since 2014, seven additional genes have been associated with ALS (MATR3, CHCHD10, TBK1, TUBA4A, NEK1, C21orf2, and CCNF), all of which were identified by genome-wide association studies, whole genome studies, or exome sequencing technologies. Each of the seven novel genes code for proteins associated with one or more molecular pathways known to be involved in ALS. These pathways include dysfunction in global protein homoeostasis resulting from abnormal protein aggregation or a defect in the protein clearance pathway, mitochondrial dysfunction, altered RNA metabolism, impaired cytoskeletal integrity, altered axonal transport dynamics, and DNA damage accumulation due to defective DNA repair. Because t...
Source: The Lancet Neurology - Category: Neurology Source Type: research