@article{10902/24038,
year = {2021},
month = {2},
url = {http://hdl.handle.net/10902/24038},
abstract = {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 to 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.},
organization = {FUNDING: This research was supported by the Intramural Research Program of the National Institutes of Health (National Institute on Aging, National Institute of Neurological Disorders and Stroke; project numbers: 1ZIAAG000935 [PI Bryan J. Traynor], 1ZIANS003154 [PI Sonja W. Scholz], 1ZIANS0030033 and 1ZIANS003034 [David S. Goldstein]). Drs. Sidransky, Lopez, and Tayebi were supported by the Intramural Research Program of the National Human Genome Research Institute. This research was supported by Italian Ministry of Health (Ricerca Corrente). Dr. Hickman is a Columbia University Irving Medical Center ADRC Research Education Component trainee (P30 AG066462-01 PI: Small, Scott), and is supported by grants from the Hereditary Disease Foundation and Huntington Disease Society of America. Dr Rowe is supported by the Wellcome Trust (103838) and National Institute for Health Research Cambridge Biomedical Research Centre. Dr. Landers was supported by the National Institutes of Health/National Institute of Neurological Disorders (R01NS073873). The American Genome Center is supported by an NHLBI grant: IAA-A-HL-007.001. The sequencing activities at NYGC were supported by the ALS Association (Grant # 19-SI-459) and The Tow Foundation.},
publisher = {Elsevier (Cell Press)},
publisher = {Neuron, Volume 109, Issue 3, 3 February 2021, Pages 448-460.e4},
title = {Pathogenic huntingtin repeat expansions in patients with frontotemporal dementia and amyotrophic lateral sclerosis},
author = {Dewan, Ramita and Chia, Ruth and Ding, Jinhui and Hickman, Richard A. and Stein, Thor D. and Abramzon, Yevgeniya and Ahmed, Sarah and Sabir, Marya S. and Portley, Makayla K. and Tucci, Arianna and Ibañez, Kristina and Shankaracharya, F.N.U. and Keagle, Pamela and Rossi, Giacomina and Caroppo, Paola and Tagliavini, Fabrizio and Waldo, Maria L. and Johansson, Per M. and Nilsson, Christer F. and Infante Ceberio, Jon},
}