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Nat Neurosci. 2013 Jul;16(7):851-5. doi: 10.1038/nn.3412. Epub 2013 May 26.

Exome sequencing to identify de novo mutations in sporadic ALS trios.

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1
Department of Genetics, Stanford University School of Medicine, Stanford, California, USA. chesi@stanford.edu

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.

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PMID:
23708140
PMCID:
PMC3709464
DOI:
10.1038/nn.3412
[Indexed for MEDLINE]
Free PMC Article
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