Novel TBK1 truncating mutation in a familial amyotrophic lateral sclerosis patient of Chinese origin.
Missense and frameshift mutations in TRAF family member-associated NF-kappa-B activator (TANK)-binding kinase 1 (TBK1) have been reported in European sporadic and familial amyotrophic lateral sclerosis (ALS) cohorts. To assess the role of TBK1 in ALS patient cohorts of wider ancestry, we have analyzed whole-exome sequence data from an Australian cohort of familial ALS (FALS) patients and controls. We identified a novel TBK1 deletion (c.1197delC) in a FALS patient of Chinese origin. This frameshift mutation (p.L399fs) likely results in a truncated protein that lacks functional domains required for adapter protein binding, as well as protein activation and structural integrity. No novel or reported TBK1 mutations were identified in FALS patients of European ancestry. This is the first report of a TBK1 mutation in an ALS patient of Asian origin and indicates that sequence variations in TBK1 are a rare cause of FALS in Australia.
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.
Kelly L
KL
Williams
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.
Emily P
EP
McCann
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.
Jennifer A
JA
Fifita
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.
Katharine
K
Zhang
Department of Endocrinology and Diabetes, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia; University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia.
Emma L
EL
Duncan
University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia.
Paul J
PJ
Leo
University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia.
Mhairi
M
Marshall
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.
Dominic B
DB
Rowe
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia; University of Sydney, ANZAC Research Institute, Concord Hospital, Sydney, New South Wales, Australia.
Garth A
GA
Nicholson
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia. Electronic address: ian.blair@mq.edu.au.
Ian P
IP
Blair
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D015331:Cohort Studies; D016368:Frameshift Mutation; D056726:Genetic Association Studies; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human
Amyotrophic lateral sclerosis; Frameshift; Gene; Motor neuron disease; Mutation; TBK1