28
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

      , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
      Neuron
      Elsevier BV
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          <p id="P3">To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified <i>kinesin family member 5A (KIF5A)</i> as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases, hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth Type 2 (CMT2). In contrast, ALS associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss of function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in <i>KIF5A</i> and strengthen the role of cytoskeletal defects in the pathogenesis of ALS. </p><p id="P4">Using large-scale genome-wide association study and exome sequencing, we identified <i>KIF5A</i> as a novel gene associated with ALS. Our data broaden the phenotype resulting from mutations in <i>KIF5A</i> and highlight the importance of cytoskeletal defects in the pathogenesis of ALS. </p>

          Related collections

          Author and article information

          Journal
          Neuron
          Neuron
          Elsevier BV
          08966273
          March 2018
          March 2018
          : 97
          : 6
          : 1268-1283.e6
          Article
          10.1016/j.neuron.2018.02.027
          5867896
          29566793
          0c6fc9a8-a868-4e3e-8bc6-920605ec045e
          © 2018

          https://www.elsevier.com/tdm/userlicense/1.0/

          http://www.elsevier.com/open-access/userlicense/1.0/

          History

          Comments

          Comment on this article