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dc.contributor.authorFraenkel, Ernest
dc.date.accessioned2023-01-31T18:16:29Z
dc.date.available2023-01-31T18:16:29Z
dc.date.issued2021
dc.identifier.urihttps://hdl.handle.net/1721.1/147812
dc.description.abstractWe 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.en_US
dc.language.isoen
dc.publisherElsevier BVen_US
dc.relation.isversionof10.1016/J.NEURON.2020.11.005en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titlePathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosisen_US
dc.typeArticleen_US
dc.identifier.citationFraenkel, Ernest. 2021. "Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis." Neuron, 109 (3).
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.relation.journalNeuronen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2023-01-31T18:02:47Z
dspace.orderedauthorsDewan, R; Chia, R; Ding, J; Hickman, RA; Stein, TD; Abramzon, Y; Ahmed, S; Sabir, MS; Portley, MK; Tucci, A; Ibáñez, K; Shankaracharya, FNU; Keagle, P; Rossi, G; Caroppo, P; Tagliavini, F; Waldo, ML; Johansson, PM; Nilsson, CF; Rowe, JB; Benussi, L; Binetti, G; Ghidoni, R; Jabbari, E; Viollet, C; Glass, JD; Singleton, AB; Silani, V; Ross, OA; Ryten, M; Torkamani, A; Tanaka, T; Ferrucci, L; Resnick, SM; Pickering-Brown, S; Brady, CB; Kowal, N; Hardy, JA; Van Deerlin, V; Vonsattel, JP; Harms, MB; Morris, HR; Ferrari, R; Landers, JE; Chiò, A; Gibbs, JR; Dalgard, CL; Scholz, SW; Traynor, BJ; Adeleye, A; Alba, C; Bacikova, D; Hupalo, DN; Martinez, EM; Pollard, HB; Sukumar, G; Soltis, AR; Tuck, M; Zhang, X; Wilkerson, MD; Smith, BN; Ticozzi, N; Fallini, C; Gkazi, AS; Topp, SD; Kost, J; Scotter, EL; Kenna, KP; Miller, JW; Tiloca, C; Vance, C; Danielson, EW; Troakes, C; Colombrita, C; Al-Sarraj, S; Lewis, EA; King, A; Calini, D; Pensato, V; Castellotti, B; de Belleroche, J; Baas, F; ten Asbroek, ALMA; Sapp, PC; McKenna-Yasek, D; McLaughlin, RL; Polak, M; Asress, S; Esteban-Pérez, J; Muñoz-Blanco, JL; Stevic, Z; D’Alfonso, S; Mazzini, L; Comi, GP; Del Bo, R; Ceroni, M; Gagliardi, S; Querin, G; Bertolin, C; van Rheenen, W; Diekstra, FP; Rademakers, R; van Blitterswijk, M; Boylan, KB; Lauria, G; Duga, S; Corti, S; Cereda, C; Corrado, L; Sorarù, G; Williams, KL; Nicholson, GA; Blair, IP; Leblond-Manry, C; Rouleau, GA; Hardiman, O; Morrison, KE; Veldink, JH; van den Berg, LH; Al-Chalabi, A; Pall, H; Shaw, PJ; Turner, MR; Talbot, K; Taroni, F; García-Redondo, A; Wu, Z; Gellera, C; Ratti, A; Brown, RH; Shaw, CE; Ambrose, JC; Arumugam, P; Baple, EL; Bleda, M; Boardman-Pretty, F; Boissiere, JM; Boustred, CR; Brittain, H; Caulfield, MJ; Chan, GC; Craig, CEH; Daugherty, LC; de Burca, A; Devereau, A; Elgar, G; Foulger, RE; Fowler, T; Furió-Tarí, P; Hackett, JM; Halai, D; Hamblin, A; Henderson, S; Holman, JE; Hubbard, TJP; Jackson, R; Jones, LJ; Kasperaviciute, D; Kayikci, M; Lahnstein, L; Lawson, K; Leigh, SEA; Leong, IUS; Lopez, JF; Maleady-Crowe, F; Mason, J; McDonagh, EM; Moutsianas, L; Mueller, M; Murugaesu, N; Need, AC; Odhams, CA; Patch, C; Perez-Gil, D; Polychronopoulos, D; Pullinger, J; Rahim, T; Rendon, A; Riesgo-Ferreiro, P; Rogers, T; Savage, K; Sawant, K; Scott, RH; Siddiq, A; Sieghart, A; Smedley, D; Smith, KR; Sosinsky, A; Spooner, W; Stevens, HE; Stuckey, A; Sultana, R; Thomas, ERA; Thompson, SR; Tregidgo, C; Walsh, E; Watters, SA; Welland, MJ; Williams, E; Witkowska, K; Wood, SM; Zarowiecki, M; Arepalli, S; Auluck, P; Baloh, RH; Bowser, R; Brice, A; Broach, J; Camu, W; Chiò, A; Cooper-Knock, J; Corcia, P; Drepper, C; Drory, VE; Dunckley, TL; Faghri, F; Farren, J; Feldman, E; Floeter, MK; Fratta, P; Gerhard, G; Gibson, SB; Goutman, SA; Heiman-Patterson, TD; Hernandez, DG; Hoover, B; Jansson, L; Kamel, F; Kirby, J; Kowall, NW; Laaksovirta, H; Landi, F; Le Ber, I; Lumbroso, S; MacGowan, DJL; Maragakis, NJ; Mora, G; Mouzat, K; Myllykangas, L; Nalls, MA; Orrell, RW; Ostrow, LW; Pamphlett, R; Pioro, E; Pulst, SM; Ravits, JM; Renton, AE; Robberecht, W; Robey, I; Rogaeva, E; Rothstein, JD; Sendtner, M; Shaw, PJ; Sidle, KC; Simmons, Z; Stone, DJ; Tienari, PJ; Trojanowski, JQ; Troncoso, JC; Valori, M; Van Damme, P; Van Den Bosch, L; Zinman, L; Albani, D; Borroni, B; Padovani, A; Bruni, A; Clarimon, J; Dols-Icardo, O; Illán-Gala, I; Lleó, A; Danek, A; Galimberti, D; Scarpini, E; Serpente, M; Graff, C; Chiang, H-H; Khoshnood, B; Öijerstedt, L; Morris, CM; Nacmias, B; Sorbi, S; Nielsen, JE; Hjermind, LE; Novelli, V; Puca, AA; Pastor, P; Alvarez, I; Diez-Fairen, M; Aguilar, M; Perneczky, R; Diehl-Schimd, J; Rogaeva, E; Rossi, M; Ruiz, A; Boada, M; Hernández, I; Moreno-Grau, S; Schlachetzki, JC; Aarsland, D; Alba, C; Albert, MS; Al-Sarraj, S; Attems, J; Bacikova, D; Barrett, MJ; Beach, TG; Bekris, LM; Bennett, DA; Besser, LM; Bigio, EH; Black, SE; Boeve, BF; Bohannan, RC; Brett, F; Brice, A; Brunetti, M; Caraway, CA; Palma, J-A; Calvo, A; Canosa, A; Clarimon, J; Dickson, D; Diez-Fairen, M; Duyckaerts, C; Faber, K; Ferman, T; Flanagan, ME; Floris, G; Foroud, TM; Fortea, J; Gan-Or, Z; Gentleman, S; Ghetti, B; Gibbs, JR; Goate, A; Goldstein, D; González-Aramburu, I; Graff-Radford, NR; Hodges, AK; Hu, H-C; Hupalo, D; Infante, J; Iranzo, A; Kaiser, SM; Kaufmann, H; Keith, J; Kim, RC; Klein, G; Krüger, R; Kukull, W; Kuzma, A; Lage, C; Lesage, S; Lleó, A; Leverenz, JB; Logroscino, G; Lopez, G; Love, S; Mao, Q; Marti, MJ; Martinez-McGrath, E; Masellis, M; Masliah, E; May, P; McKeith, I; Mesulam, M-M; Monuki, ES; Morris, CM; Newell, KL; Norcliffe-Kaufmann, L; Palmer, L; Pastor, P; Perkins, M; Pletnikova, O; Molina-Porcel, L; Renton, AE; Reynolds, RH; Rodríguez-Rodríguez, E; Rogaeva, E; Rohrer, JD; Sanchez-Juan, P; Scherzer, CR; Serrano, GE; Shakkottai, V; Sidransky, E; Tayebi, N; Thomas, AJ; Tilley, BS; Troakes, C; Troncoso, JC; Walton, RL; Woltjer, R; Wszolek, ZK; Xiromerisiou, G; Zecca, C; Phatnani, H; Kwan, J; Sareen, D; Broach, JR; Simmons, Z; Arcila-Londono, X; Lee, EB; Shneider, NA; Fraenkel, E; Ostrow, LW; Baas, F; Zaitlen, N; Berry, JD; Malaspina, A; Fratta, P; Cox, GA; Thompson, LM; Finkbeiner, S; Dardiotis, E; Miller, TM; Chandran, S; Pal, S; Hornstein, E; MacGowan, DJ; Heiman-Patterson, T; Hammell, MG; Patsopoulos, N; Butovsky, O; Dubnau, J; Nath, A; Bowser, R; Harms, M; Aronica, E; Poss, M; Phillips-Cremins, J; Crary, J; Atassi, N; Lange, DJ; Adams, DJ; Stefanis, L; Gotkine, M; Baloh, RH; Babu, S; Raj, T; Paganoni, S; Shalem, O; Smith, C; Zhang, B; Harris, B; Broce, I; Drory, V; Ravits, J; McMillan, C; Menon, V; Wu, L; Altschuler, S; Amar, K; Archibald, N; Bandmann, O; Capps, E; Church, A; Coebergh, J; Costantini, A; Critchley, P; Ghosh, BCP; Hu, MTM; Kobylecki, C; Leigh, PN; Mann, C; Massey, LA; Morris, HR; Nath, U; Pavese, N; Paviour, D; Sharma, J; Vaughan, Jen_US
dspace.date.submission2023-01-31T18:02:49Z
mit.journal.volume109en_US
mit.journal.issue3en_US
mit.licensePUBLISHER_CC
mit.metadata.statusAuthority Work and Publication Information Neededen_US


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