RT Journal Article
SR Electronic
T1 Genetics insight into the amyotrophic lateral sclerosis/frontotemporal dementia spectrum
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 145
OP 154
DO 10.1136/jmedgenet-2016-104271
VO 54
IS 3
A1 Ai-Ling Ji
A1 Xia Zhang
A1 Wei-Wei Chen
A1 Wen-Juan Huang
YR 2017
UL http://jmg.bmj.com/content/54/3/145.abstract
AB 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 of chromosome 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 ALS and FTD 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 of C9orf72 mutations, 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.