Novel TBK1 truncating mutation in a familial amyotrophic lateral sclerosis patient of Chinese origin

Abstract 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...

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Bibliographic Details
Published in:Neurobiology of aging 2015-12, Vol.36 (12), p.3334.e1-3334.e5
Main Authors: Williams, Kelly L, McCann, Emily P, Fifita, Jennifer A, Zhang, Katharine, Duncan, Emma L, Leo, Paul J, Marshall, Mhairi, Rowe, Dominic B, Nicholson, Garth A, Blair, Ian P
Format: Article
Language:English
Subjects:
Amyotrophic lateral sclerosis
Amyotrophic Lateral Sclerosis - genetics
Asian Continental Ancestry Group - genetics
Cohort Studies
Frameshift
Frameshift Mutation
Gene
Genetic Association Studies
Humans
Internal Medicine
Motor neuron disease
Mutation
Neurology
Protein-Serine-Threonine Kinases - genetics
TBK1
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Summary:Abstract 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.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2015.08.013