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

Shu, Shi; Li, Xiao Ling; Liu, Qing; Liu, Fang; Cui, Bo; Liu, Ming-Sheng; Li, Xiao Guang; Zhang, Xue

doi:10.1080/21678421.2016.1183681

Cited by 16 publications

(11 citation statements)

References 11 publications

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“…Several previous studies have reported dominant variants in TBK1 in cases of MND, FTD, and MND-FTD, accounting for approximately 1% of all cases ( Borghero et al., 2016 , Cirulli et al., 2015 , Exome Aggregation Consortium (ExAC) , Freischmidt et al., 2015 , Gijselinck et al., 2015 , Le Ber et al., 2015 , Pottier et al., 2015 , Shu et al., 2016 , Tsai et al., 2016 , van Rheenen et al., 2016 , Williams et al., 2015 ). In our study, we observed 6 cases and 1 control with a rare stop-gain, splice site frameshift, or missense variant in TBK1 ( Section 2.4 ; Table 2 and Supplementary Table 5 ; Fisher's p = 0.080).…”

Section: Resultsmentioning

confidence: 99%

Genetic epidemiology of motor neuron disease-associated variants in the Scottish population

Black

Leighton

Cleary

et al. 2017

Neurobiology of Aging

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Genetic understanding of motor neuron disease (MND) has evolved greatly in the past 10 years, including the recent identification of association between MND and variants in TBK1 and NEK1. Our aim was to determine the frequency of pathogenic variants in known MND genes and to assess whether variants in TBK1 and NEK1 contribute to the burden of MND in the Scottish population. SOD1, TARDBP, OPTN, TBK1, and NEK1 were sequenced in 441 cases and 400 controls. In addition to 44 cases known to carry a C9orf72 hexanucleotide repeat expansion, we identified 31 cases and 2 controls that carried a loss-of-function or pathogenic variant. Loss-of-function variants were found in TBK1 in 3 cases and no controls and, separately, in NEK1 in 3 cases and no controls. This study provides an accurate description of the genetic epidemiology of MND in Scotland and provides support for the contribution of both TBK1 and NEK1 to MND susceptibility in the Scottish population.

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Section: Resultsmentioning

confidence: 99%

Genetic epidemiology of motor neuron disease-associated variants in the Scottish population

Black

Leighton

Cleary

et al. 2017

Neurobiology of Aging

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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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“…[13,14,[21][22][23][29][30][31][32][33]. TBK1 can be considered an established causal gene, based on conclusive linkage in multiple families, replication in many cohorts from different origin, and supportive functional evidence suggesting a role in autophagy and neuroinflammation.…”

mentioning

confidence: 99%

ALS Genes in the Genomic Era and their Implications for FTD

2018

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Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease, characterized genetically by a disproportionately large contribution of rare genetic variation. Driven by advances in massive parallel sequencing and applied on large patient-control cohorts, systematic identification of these rare variants that make up the genetic architecture of ALS became feasible. In this review paper, we present a comprehensive overview of recently proposed ALS genes that were identified based on rare genetic variants (TBK1, CHCHD10, TUBA4A, CCNF, MATR3, NEK1, C21orf2, ANXA11, TIA1) and their potential relevance to frontotemporal dementia genetic etiology. As more causal and risk genes are identified, it has become apparent that affected individuals can carry multiple disease-associated variants. In light of this observation, we discuss the oligogenic architecture of ALS. To end, we highlight emerging key molecular processes and opportunities for therapy.

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

Cited by 16 publications

References 11 publications

Genetic epidemiology of motor neuron disease-associated variants in the Scottish population

Genetic epidemiology of motor neuron disease-associated variants in the Scottish population

The epidemiology and genetics of Amyotrophic lateral sclerosis in China

ALS Genes in the Genomic Era and their Implications for FTD

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