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25 January 2021
Article (Scientific journals)
Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.
Dewan, Ramita; Chia, Ruth; Ding, Jinhui et al.
2021In Neuron, 109 (3), p. 448-460
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Keywords :
amyotrophic lateral sclerosis; frontotemporal dementia; huntingtin; repeat expansions; whole-genome sequencing
Abstract :
[en] We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)
- Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group)
Disciplines :
Genetics & genetic processes
Author, co-author :
Dewan, Ramita
Chia, Ruth
Ding, Jinhui
Hickman, Richard A.
Stein, Thor D.
Abramzon, Yevgeniya
Ahmed, Sarah
Sabir, Marya S.
Portley, Makayla K.
Tucci, Arianna
Ibáñez, Kristina
Shankaracharya, F. N. U.
Keagle, Pamela
Rossi, Giacomina
Caroppo, Paola
Tagliavini, Fabrizio
Waldo, Maria L.
Johansson, Per M.
Nilsson, Christer F.
May, Patrick ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
Krüger, Rejko ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience
Rowe, James B.
Benussi, Luisa
Binetti, Giuliano
Ghidoni, Roberta
Jabbari, Edwin
Viollet, Coralie
Glass, Jonathan D.
Singleton, Andrew B.
Silani, Vincenzo
Ross, Owen A.
Ryten, Mina
Torkamani, Ali
Tanaka, Toshiko
Ferrucci, Luigi
Resnick, Susan M.
Pickering-Brown, Stuart
Brady, Christopher B.
Kowal, Neil
Hardy, John A.
Van Deerlin, Vivianna
Vonsattel, Jean Paul
Harms, Matthew B.
Morris, Huw R.
Ferrari, Raffaele
Landers, John E.
Chiò, Adriano
Gibbs, J. Raphael
Dalgard, Clifton L.
Scholz, Sonja W.
Traynor, Bryan J.
More authors (41 more) Less
External co-authors :
Language :
Title :
Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.
Publication date :
03 February 2021
Journal title :
Publisher :
Cell Press, Cambridge, United States - Massachusetts
Volume :
Issue :
Pages :
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
FnR Project :
FNR11264123 > Rejko Krüger > > Ncer-pd > 01/01/2015 > 30/11/2020 > 2015
Commentary :
Published by Elsevier Inc.


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