@article{8f2e1376621042828ec1912f8f426531,
title = "Exome sequencing to identify de novo mutations in sporadic ALS trios",
abstract = "Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease whose causes are still poorly understood. To identify additional genetic risk factors, we assessed the role of de novo mutations in ALS by sequencing the exomes of 47 ALS patients and both of their unaffected parents (n = 141 exomes). We found that amino acid-altering de novo mutations were enriched in genes encoding chromatin regulators, including the neuronal chromatin remodeling complex (nBAF) component SS18L1 (also known as CREST). CREST mutations inhibited activity-dependent neurite outgrowth in primary neurons, and CREST associated with the ALS protein FUS. These findings expand our understanding of the ALS genetic landscape and provide a resource for future studies into the pathogenic mechanisms contributing to sporadic ALS.",
author = "Alessandra Chesi and Staahl, {Brett T.} and Ana Jovi{\v c}i{\'c} and Julien Couthouis and Maria Fasolino and Raphael, {Alya R.} and Tomohiro Yamazaki and Laura Elias and Meraida Polak and Crystal Kelly and Williams, {Kelly L.} and Fifita, {Jennifer A.} and Maragakis, {Nicholas J.} and Nicholson, {Garth A.} and King, {Oliver D.} and Robin Reed and Crabtree, {Gerald R.} and Blair, {Ian P.} and Glass, {Jonathan D.} and Gitler, {Aaron D.}",
note = "Funding Information: This work was also supported by the National Health and Medical Research Council of Australia (1004670, 511941) and the Motor Neurone Disease Research Institute of Australia. Funding Information: This work was supported by a US National Institutes of Health Director{\textquoteright}s New Innovator Award 1DP2OD004417 (A.D.G.), grants from the US National Institutes of Health (1R01NS065317 to A.D.G., R01NS046789 to G.R.C. and 5U01NS062713 to N.J.M.) and the Department of Defense ALS Research Program (N.J.M.). A.D.G. received funding from the Biogen Idec ALS genome sequencing consortium. A.D.G. received funding from The Pew Charitable Trusts and the Rita Allen Foundation. G.R.C. receives funding from the Howard Hughes Medical Institute. A.D.G. and J.D.G. are supported by the Packard Center for ALS Research at Johns Hopkins.",
year = "2013",
month = jul,
doi = "10.1038/nn.3412",
language = "English (US)",
volume = "16",
pages = "851--855",
journal = "Nature neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "7",
}