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Exome sequencing uncovers hidden pathways in familial and sporadic ALS

Nature Neuroscience volume 18, pages 611–613 (2015)Cite this article

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Amyotrophic lateral sclerosis (ALS) is a complex and as yet untreatable neurodegenerative disorder. We discuss two examples of exome sequencing in large international collections of familial and sporadic ALS cases that are revealing new and potentially treatable pathways, such as those involving autophagy and neuroinflammation.

The most significant advances in our understanding of the etiology of neurodegenerative disorders, and perhaps all neurological disorders, have come from the identification of disease-causing genes. Most Mendelian genes have now been identified, forming a framework of disease pathways. Yet there are major challenges ahead in the investigation of genetically diverse, more common disorders such as ALS that are likely to be caused by an intricate combination of rare and common genetic variation, together with environmental and stochastic factors.

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Figure 1: Progress of genetic findings related to ALS etiology and pathogenesis.

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Authors and Affiliations

  1. Conceição Bettencourt and Henry Houlden are in the Department of Molecular Neuroscience and the Medical Research Council Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery and University College London Institute of Neurology, London, UK.,

    Conceição Bettencourt & Henry Houlden

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  1. Conceição Bettencourt
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  2. Henry Houlden
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Correspondence to Henry Houlden.

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Bettencourt, C., Houlden, H. Exome sequencing uncovers hidden pathways in familial and sporadic ALS. Nat Neurosci 18, 611–613 (2015). https://doi.org/10.1038/nn.4012

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