title: Genetics insight into the amyotrophic lateral sclerosis/frontotemporal dementia spectrum.
abstract: Recent genetic discoveries have dramatically changed our understanding of two major neurodegenerative conditions. Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are common, devastating diseases of the brain. For decades, ALS and FTD were classified as movement and cognitive disorders, respectively, due to their distinct clinical phenotypes. The recent identification ofchromosome 9 open reading frame 72(C9orf72) as the major gene causative of familial forms of ALS and FTD uncovered a new reality of a continuous FTD/ALS spectrum. The finding that up to 50% of all patients present some degree of ALSandFTD phenotypes supports this ALS/FTD continuum. Now >100 genes are known to contribute to ALS/FTD, with a few major contributors that are reviewed below. The low penetrance ofC9orf72mutations, its contribution to sporadic cases, and its combination with other genes support an oligogenic model where two or more genes contribute to disease risk, onset, progression and phenotype: from 'pure' ALS or FTD to combined ALS/FTD. These advances in the genetics of ALS/FTD will soon lead to a better mechanistic understanding of the pathobiology of the disease, which should result in the development of effective therapies in the near future.
authors.affiliation: Department of Neurology, The Third People Hospital of Xuzhou, Xuzhou, China.
authors.forename: Ai-Ling
authors.initials: AL
authors.lastname: Ji
authors.affiliation: Department of Neurology, Xuzhou Central Hospital, Xuzhou, China.|The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, China.|Xuzhou Clinical School of Xuzhou Medical College, Xuzhou, China.|Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, Xuzhou, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Xuzhou Central Hospital, Xuzhou, China.|The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, China.|Xuzhou Clinical School of Xuzhou Medical College, Xuzhou, China.|Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, Xuzhou, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Chen
authors.affiliation: Department of Neurology, Xuzhou Central Hospital, Xuzhou, China.|The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, China.|Xuzhou Clinical School of Xuzhou Medical College, Xuzhou, China.|Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, Xuzhou, China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Huang
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000473:pathology; D000073885:C9orf72 Protein / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009154:Mutation
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D004268:DNA-Binding Proteins
keywords: Genetic screening/counselling; Genetics; Genome-wide; Neurology; Neuromuscular disease