Exome sequencing to identify de novo mutations in sporadic ALS trios

Alessandra Chesi*, Brett T. Staahl, Ana Jovičić, Julien Couthouis, Maria Fasolino, Alya R. Raphael, Tomohiro Yamazaki, Laura Elias, Meraida Polak, Crystal Kelly, Kelly L. Williams, Jennifer A. Fifita, Nicholas J. Maragakis, Garth A. Nicholson, Oliver D. King, Robin Reed, Gerald R. Crabtree, Ian P. Blair, Jonathan D. Glass, Aaron D. Gitler

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

117 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)851-855
Number of pages5
JournalNature Neuroscience
Issue number7
Publication statusPublished - 2013


Dive into the research topics of 'Exome sequencing to identify de novo mutations in sporadic ALS trios'. Together they form a unique fingerprint.

Cite this