Dataset Information

Rare TBK1 variants in patients with frontotemporal dementia and amyotrophic lateral sclerosis in a Chinese cohort.

ABSTRACT: Background:The TANK-Binding Kinase 1 (TBK1) gene has recently been identified as the third or fourth most frequent cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The aim of this study was to assess the genetic contribution of TBK1 in a Chinese cohort. Methods:A total of 270 cases with ALS, FTD, or their combination were recruited into this study. All the coding exons of TBK1 and intron-exon boundaries were sequenced using Sanger sequencing. The frequency of TBK1 variants and the correlation with clinical phenotypes were analyzed. Results:A novel mutation (c.1959_1960insGT, p.E653fs) was identified in a sporadic case with semantic dementia, secondarily developing ALS. Another novel variant (c.2063_2064delTT, p.L688Rfs*14) was found in an ALS-FTD family. Totally, the TBK1 variants could only account for 0.7% of cases. Conclusions:This study enlarges the genetic and phenotypic spectrum of TBK1 mutation in a Chinese cohort. Our data indicates that TBK1 mutation is not a common cause for ALS and FTD in Chinese patients.

SUBMITTER: Jiao B

PROVIDER: S-EPMC6278101 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Rare <i>TBK1</i> variants in patients with frontotemporal dementia and amyotrophic lateral sclerosis in a Chinese cohort.

Jiao Bin B Sun Qiying Q Yuan Zhenhua Z Wang Junling J Zhou Lin L Yan Xinxiang X Tang Beisha B Shen Lu L

Translational neurodegeneration 20181204

<h4>Background</h4>The TANK-Binding Kinase 1 (<i>TBK1</i>) gene has recently been identified as the third or fourth most frequent cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The aim of this study was to assess the genetic contribution of <i>TBK1</i> in a Chinese cohort.<h4>Methods</h4>A total of 270 cases with ALS, FTD, or their combination were recruited into this study. All the coding exons of <i>TBK1</i> and intron-exon boundaries were sequenced using Sange ...[more]

PMID: 30534373

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Project description:Amyotrophic lateral sclerosis and frontotemporal dementia are two progressive, adult onset neurodegenerative diseases, caused by the cell death of motor neurons in the motor cortex and spinal cord and cortical neurons in the frontal and temporal lobes, respectively. Whilst these have previously appeared to be quite distinct disorders, in terms of areas affected and clinical symptoms, identification of cognitive dysfunction as a component of amyotrophic lateral sclerosis (ALS), with some patients presenting with both ALS and FTD, overlapping features of neuropathology and the ongoing discoveries that a significant proportion of the genes underlying the familial forms of the disease are the same, has led to ALS and FTD being described as a disease spectrum. Many of these genes encode proteins in common biological pathways including RNA processing, autophagy, ubiquitin proteasome system, unfolded protein response and intracellular trafficking. This article provides an overview of the ALS-FTD genes before summarizing other known ALS and FTD causing genes where mutations have been found primarily in patients of one disease and rarely in the other. In discussing these genes, the review highlights the similarity of biological pathways in which the encoded proteins function and the interactions that occur between these proteins, whilst recognizing the distinctions of MAPT-related FTD and SOD1-related ALS. However, mutations in all of these genes result in similar pathology including protein aggregation and neuroinflammation, highlighting that multiple different mechanisms lead to common downstream effects and neuronal loss. Next generation sequencing has had a significant impact on the identification of genes associated with both diseases, and has also highlighted the widening clinical phenotypes associated with variants in these ALS and FTD genes. It is hoped that the large sequencing initiatives currently underway in ALS and FTD will begin to uncover why different diseases are associated with mutations within a single gene, especially as a personalized medicine approach to therapy, based on a patient's genetics, approaches the clinic.

Dataset Information

Rare TBK1 variants in patients with frontotemporal dementia and amyotrophic lateral sclerosis in a Chinese cohort.

Publications

Rare <i>TBK1</i> variants in patients with frontotemporal dementia and amyotrophic lateral sclerosis in a Chinese cohort.

Similar Datasets

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