title: State of play in amyotrophic lateral sclerosis genetics.
abstract: Considerable progress has been made in unraveling the genetic etiology of amyotrophic lateral sclerosis (ALS), the most common form of adult-onset motor neuron disease and the third most common neurodegenerative disease overall. Here we review genes implicated in the pathogenesis of motor neuron degeneration and how this new information is changing the way we think about this fatal disorder. Specifically, we summarize current literature of the major genes underlying ALS, SOD1, TARDBP, FUS, OPTN, VCP, UBQLN2, C9ORF72 and PFN1, and evaluate the information being gleaned from genome-wide association studies. We also outline emerging themes in ALS research, such as next-generation sequencing approaches to identify de novo mutations, the genetic convergence of familial and sporadic ALS, the proposed oligogenic basis for the disease, and how each new genetic discovery is broadening the phenotype associated with the clinical entity we know as ALS.
authors.affiliation: Neuromuscular Diseases Research Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Alan E
authors.initials: AE
authors.lastname: Renton
authors.affiliation: Rita Levi Montalcini Department of Neuroscience, University of Turin, Turin, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Chiò
authors.affiliation: 1] Neuromuscular Diseases Research Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA. [2] Department of Neurology, Brain Sciences Institute, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Traynor
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000071183:Autophagy-Related Proteins; D000073885:C9orf72 Protein; D018797:Cell Cycle Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D026901:Membrane Transport Proteins; D009154:Mutation / Q000235:genetics; D051304:Profilins / Q000235:genetics; D011506:Proteins; D034702:RNA-Binding Protein FUS / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D035582:Transcription Factor TFIIIA / Q000235:genetics; D014452:Ubiquitins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D026901:Membrane Transport Proteins; C409460:OPTN protein, human; C495738:PFN1 protein, human; D051304:Profilins; D011506:Proteins; D034702:RNA-Binding Protein FUS; C000606290:SOD1 protein, human; D035582:Transcription Factor TFIIIA; C405662:UBQLN2 protein, human; D014452:Ubiquitins; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1