In 2012, researchers published extensively on the genetic and clinicopathological characterization of patients with the newly discovered C9ORF72 repeat expansions, which cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Novel ALS-linked genes and genetic modifiers were identified through screening in animal models and patients.
This is a preview of subscription content, log in via an institution to check access.
References
DeJesus-Hernandez, M. et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72, 245–256 (2011).
Renton, A. E. et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72, 257–268 (2011).
Majounie, E. et al. Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. Lancet Neurol. 11, 323–330 (2012).
van Blitterswijk, M., DeJesus-Hernandez, M. & Rademakers, R. How do C9ORF72 repeat expansions cause amyotrophic lateral sclerosis and frontotemporal dementia: can we learn from other noncoding repeat expansion disorders? Curr. Opin. Neurol. 25, 689–700 (2012).
Kiernan, M. C. et al. Amyotrophic lateral sclerosis. Lancet 377, 942–955 (2011).
Hodges, J. Familial frontotemporal dementia and amyotrophic lateral sclerosis associated with the C9ORF72 hexanucleotide repeat. Brain 135, 652–655 (2012).
van Blitterswijk, M. et al. Evidence for an oligogenic basis of amyotrophic lateral sclerosis. Hum. Mol. Genet. 21, 3776–3784 (2012).
Wu, C. H. et al. Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature 488, 499–503 (2012).
Van Hoecke, A. et al. EPHA4 is a disease modifier of amyotrophic lateral sclerosis in animal models and in humans. Nat. Med. 18, 1418–1422 (2012).
Armakola, M. et al. Inhibition of RNA lariat debranching enzyme suppresses TDP-43 toxicity in ALS disease models. Nat. Genet. 44, 1302–1309 (2012).
Acknowledgements
R. Rademakers is currently funded by NIH grants P50 AG016574, R01 AG026251, R01 NS065782 and R01 NS080882, the ALS Therapy Alliance and the Consortium for Frontotemporal Dementia Research.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
R. Rademakers holds a patent on methods to screen for the hexanucleotide repeat expansion in the C9ORF72 gene. M. van Blitterswijk declares no competing interests.
Rights and permissions
About this article
Cite this article
Rademakers, R., van Blitterswijk, M. Novel causal genes and disease modifiers. Nat Rev Neurol 9, 63–64 (2013). https://doi.org/10.1038/nrneurol.2012.276
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrneurol.2012.276
- Springer Nature Limited
This article is cited by
-
Role of the C9ORF72 Gene in the Pathogenesis of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
Neuroscience Bulletin (2020)
-
Conserved DNA methylation combined with differential frontal cortex and cerebellar expression distinguishes C9orf72-associated and sporadic ALS, and implicates SERPINA1 in disease
Acta Neuropathologica (2017)
-
The ALS/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to regulate the autophagy-lysosome pathway
Acta Neuropathologica Communications (2016)
-
ALS and FTD: an epigenetic perspective
Acta Neuropathologica (2016)