Mutational analysis of TBK1 in Taiwanese patients with amyotrophic lateral sclerosis

Tsai, Pei‐Chien; Liu, Yi‐Chien; Lin, Kon‐Ping; Liu, Yo‐Tsen; Liao, Yi‐Chu; Hsiao, Cheng-Tsung; Soong, Bing‐Wen; Yip, Ping-Keung; Lee, Yi‐Chung

doi:10.1016/j.neurobiolaging.2015.12.022

Cited by 51 publications

(21 citation statements)

References 29 publications

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“…We found two SALS patients (0.7%) with unreported missense variants in TBK1, indicating that TBK1 mutation is infrequent in the Chinese population. Our results are consistent with the most recent study from Taiwan, which also reported a low frequency of the TBK1 mutation in Taiwanese (0.5%; 1/207) (8). In a Caucasian SALS population, the frequency of TBK1 variants identified as an ALS gene is about 1%$1.8% (5,6).…”

Section: Discussionsupporting

confidence: 92%

Screening of the TBK1 gene in familial and sporadic amyotrophic lateral sclerosis patients of Chinese origin

Shu¹,

Li²,

Liu

et al. 2016

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

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TANK-binding kinase 1 (TBK1) has been recently identified as a risk gene of amyotrophic lateral sclerosis (ALS). The aim of this study was to assess the contribution of TBK1 mutations to Chinese ALS patients. We sequenced the coding regions of TBK1 in a cohort of Chinese ALS patients, including 271 sporadic ALS patients and 23 familial ALS patients. Two potentially pathogenic mutations, L62P and I334T, were identified in two independent sporadic ALS patients, accounting for 0.7% of total ALS cases. Both mutations were absent from our 384 healthy controls and public single nucleotide polymorphisms databases. In conclusion, we propose that TBK1 is not a frequent causal gene in Chinese ALS patients.

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Section: Discussionsupporting

confidence: 92%

Screening of the TBK1 gene in familial and sporadic amyotrophic lateral sclerosis patients of Chinese origin

Shu¹,

Li²,

Liu

et al. 2016

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

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“…PFN1, HNRNPA1, CHCHD10, MATR3, TBK1, TUBA4A and CCNF were identified disease-causing one after another based on the analysis of WES performed in several ALS families or large cohorts of familial and sporadic ALS cases with Caucasian origin (Bannwarth et al, 2014; Cirulli et al, 2015; Freischmidt et al, 2015; Johnson et al, 2014; Kim et al, 2013, 2016; Smith et al, 2014; Wu et al, 2012). Unfortunately, mutations in above-mentioned genes are quite rare in Chinese population, suggesting genes may not be informative of the genetics in Chinese ALS patients (Chen et al, 2013; Li et al, 2016; Lin et al, 2015; Pan et al, 2017; Shen et al, 2017; Shu et al, 2016; Soong et al, 2014; Tsai et al, 2016, 2017; Xu et al, 2016; Zhou et al, 2017; Zou et al, 2013c). Targeted next-generation sequencing (NGS), a cost-effective approach for variant screening in known ALS genes, has been applied primarily in fALS and jALS (Liu et al, 2014b, 2017b).…”

Section: Genetic Characteristics Of Chinese Als Patientsmentioning

confidence: 99%

The epidemiology and genetics of Amyotrophic lateral sclerosis in China

Liu

Gao

et al. 2018

Brain Research

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder associated with loss of motor neurons. Previous knowledge of the disease has been mainly based on studies from Caucasian ALS patients of European descent. Here we review the epidemiological characteristics of ALS among the Chinese population in order to compare the similarities and differences between Chinese ALS cases and those from other countries. We describe a potential lower incidence and prevalence of ALS, a younger age of onset and a lower proportion of familial ALS cases in the Chinese population. Additionally, we highlight potential genetic differences between Chinese and Caucasian ALS patients. Most notably, the frequency of GGGGCC repeat expansions in C9ORF72 in Chinese ALS is significantly lower than in Caucasians. Since some conclusions might not be consistent across all of the studies around China to date, we suggest that it is necessary to carry out a prospective population-based study and large-scale gene sequencing around to better define epidemiological and genetic features of Chinese ALS patients.

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“…The frequency of pathogenic or potentially toxic variants of TBK1 in Korean and Japanese sALS patients was estimated to be 0.8% and 1.26% separately (Kim et al, ; Tohnai et al, ). Besides, five missense variants of TBK1 have been reported in ALS patients of Chinese population so far, among which only the patient with p.Arg444X displayed FTD‐ALS, while the others reported no cognitive dysfunction (Tsai et al, ). In addition, one frameshift mutation (p.Leu339fs) of Chinese origin was also found in an Australian cohort study of ALS (Williams et al, ).…”

Section: Discussionmentioning

confidence: 99%

Association of the TBK1 mutation p.Ile334Thr with frontotemporal dementia and literature review

Luo

et al. 2019

Molec Gen & Gen Med

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Background The mutation of TANK‐binding kinase 1 ( TBK1 ) gene has been regarded as a causative gene of frontotemporal dementia (FTD)‐amyotrophic lateral sclerosis (ALS) spectrum disease in recent years. So far, more than 70 TBK1 variants have been identified in patients with FTD‐ALS spectrum. Methods We reported a Chinese FTD patient carrying TBK1 p.Ile334Thr variant detected by target sequencing and Sanger sequencing. The patient's clinical materials were collected. The transcription and translation levels of TBK1 mutant were investigated in fibroblast by qPCR and western blot. The effects of TBK1 mutant in inflammation pathway and autophagy were detected by luciferase reporter assay and GST pull‐down assay. Results The patient was diagnosed as behavioral variant FTD (bvFTD) and displayed progressively severe cognitive impairment especially in executive function. A pattern of frontotemporal atrophy and hypometabolism was shown through MRI and PET‐CT. In vitro functional experiments of TBK1 p.Ile334Thr variant demonstrated reduced transcription and translation levels, decreased kinase activity but maintenance of interaction with optineurin. The variant was classified as likely pathogenic according to American College of Medical Genetics and Genomics guideline. Conclusion We proposed the TBK1 mutation p.Ile334Thr as a likely pathogenic variant in bvFTD which also expanded the clinical spectrum of this variant. It can partially abrogate TBK1 functions and be responsible for FTD‐ALS spectrum diseases through neuroinflammatory pathway.

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Mutational analysis of TBK1 in Taiwanese patients with amyotrophic lateral sclerosis

Cited by 51 publications

References 29 publications

Screening of the TBK1 gene in familial and sporadic amyotrophic lateral sclerosis patients of Chinese origin

Screening of the TBK1 gene in familial and sporadic amyotrophic lateral sclerosis patients of Chinese origin

The epidemiology and genetics of Amyotrophic lateral sclerosis in China

Association of the TBK1 mutation p.Ile334Thr with frontotemporal dementia and literature review

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