Journal article
Short tandem repeat expansions in sporadic amyotrophic lateral sclerosis and frontotemporal dementia
L Henden, LG Fearnley, N Grima, EP McCann, C Dobson-Stone, L Fitzpatrick, K Friend, L Hobson, SC Moi Fat, DB Rowe, S D Silva, JB Kwok, GM Halliday, MC Kiernan, S Mazumder, HC Timmins, M Zoing, R Pamphlett, L Adams, M Bahlo Show all
Science Advances | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2023
Abstract
Pathogenic short tandem repeat (STR) expansions cause over 20 neurodegenerative diseases. To determine the contribution of STRs in sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD),we used ExpansionHunter, REviewer, and polymerase chain reaction validation to assess 21 neurodegenerative diseaseassociated STRs in whole-genome sequencing data from 608 patients with sporadic ALS, 68 patients with sporadic FTD, and 4703 matched controls.We also propose a data-derived outlier detection method for defining allele thresholds in rare STRs. Excluding C9orf72 repeat expansions, 17.6% of clinically diagnosed ALS and FTD cases had at least one expanded STR allele reported to..
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Funding Acknowledgements
This study was supported by National Health and Medical Research Council of Australia grants 1095215 and 1176913 (I.P.B.);National Health and Medical Research Council of Australia grants 1037746, 1095127, and 1132524 (G.M.H. and M.C.K.);National Health and Medical Research Council of Australia grant 1153439 and fellowship 1156093 (M.C.K.);National Health and Medical Research Council of Australia grant 1195236 (M.B.);National Health and Medical Research Council of Australia fellowship 1092023 (K.L.W.);National Health and Medical Research Council of Australia fellowship 1176607 (G.M.H.);National Health and Medical Research Council of Australia fellowship 1138223 (C.D.-S.);DHB Foundation Centenary Postdoctoral Fellowship (L.G.F.);and FightMND. Motor Neurone Disease Research Australia