| Literature DB >> 30342764 |
Gijs H P Tazelaar1, Annelot M Dekker1, Joke J F A van Vugt1, Rick A van der Spek1, Henk-Jan Westeneng1, Lindy J B G Kool1, Kevin P Kenna1, Wouter van Rheenen1, Sara L Pulit1, Russell L McLaughlin2, William Sproviero3, Alfredo Iacoangeli4, Annemarie Hübers5, David Brenner5, Karen E Morrison6, Pamela J Shaw7, Christopher E Shaw7, Monica Povedano Panadés8, Jesus S Mora Pardina9, Jonathan D Glass10, Orla Hardiman11, Ammar Al-Chalabi12, Philip van Damme13, Wim Robberecht13, John E Landers14, Albert C Ludolph5, Jochen H Weishaupt5, Leonard H van den Berg1, Jan H Veldink1, Michael A van Es15.
Abstract
NIPA1 (nonimprinted in Prader-Willi/Angelman syndrome 1) mutations are known to cause hereditary spastic paraplegia type 6, a neurodegenerative disease that phenotypically overlaps to some extent with amyotrophic lateral sclerosis (ALS). Previously, a genomewide screen for copy number variants found an association with rare deletions in NIPA1 and ALS, and subsequent genetic analyses revealed that long (or expanded) polyalanine repeats in NIPA1 convey increased ALS susceptibility. We set out to perform a large-scale replication study to further investigate the role of NIPA1 polyalanine expansions with ALS, in which we characterized NIPA1 repeat size in an independent international cohort of 3955 patients with ALS and 2276 unaffected controls and combined our results with previous reports. Meta-analysis on a total of 6245 patients with ALS and 5051 controls showed an overall increased risk of ALS in those with expanded (>8) GCG repeat length (odds ratio = 1.50, p = 3.8×10-5). Together with previous reports, these findings provide evidence for an association of an expanded polyalanine repeat in NIPA1 and ALS.Entities:
Keywords: Amyotrophic lateral sclerosis; NIPA1; Repeat expansion
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Year: 2018 PMID： 30342764 PMCID： PMC7893598 DOI： 10.1016/j.neurobiolaging.2018.09.012
Source DB: PubMed Journal: Neurobiol Aging ISSN： 0197-4580 Impact factor: 4.673