التفاصيل البيبلوغرافية
| العنوان: |
TBK1 variants in Chinese patients with amyotrophic lateral sclerosis: Genetic analysis and clinical features. |
| المؤلفون: |
Zhao, Bi, Jiang, Qirui, Lin, Junyu, Wei, Qianqian, Li, Chunyu, Hou, Yanbing, Cao, Bei, Zhang, Lingyu, Ou, Ruwei, Liu, Kuncheng, Yang, Tianmi, Xiao, Yi, Shang, Huifang |
| المصدر: |
European Journal of Neurology; Oct2023, Vol. 30 Issue 10, p3079-3089, 11p |
| مصطلحات موضوعية: |
AMYOTROPHIC lateral sclerosis, CHINESE people, MISSENSE mutation, FRONTOTEMPORAL dementia, GENETIC variation |
| مستخلص: |
Background and purpose: Haploinsufficiency of TANK‐binding kinase 1 (TBK1) loss‐of‐function (LoF) variants has been shown to be pathogenic in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the genetic spectrum of TBK1 and clinical features of ALS patients with TBK1 variants remain largely unknown in Asians. Methods: Genetic analysis was performed on 2011 Chinese ALS patients. Software was used to predict the deleteriousness of missense variants in TBK1. In addition, PubMed, Embase and Web of Science were searched for related literature. Results: Twenty‐six TBK1 variants were identified in 33 of 2011 ALS patients, including six novel LoF variants (0.3%) and 20 rare missense variants, 12 of which were predicted to be deleterious (0.6%). In addition to TBK1 variants, 11 patients had other ALS‐related gene variants. Forty‐two previous studies found that the frequency of TBK1 variants was 1.81% in ALS/FTD patients. The frequency of TBK1 LoF variants in ALS was 0.5% (Asians 0.4%; Caucasian 0.6%) and that of missense variants was 0.8% (Asians 1.0%; Caucasian 0.8%). ALS patients with TBK1 LoF variants affecting the kinase domain had a significantly younger age of onset than patients carrying LoF variants affecting the coiled coil domains CCD1 and CCD2. FTD has a frequency of 10% in Caucasian ALS patients with TBK1 LoF variants, which was not found in our cohort. Conclusion: Our study expanded the genotypic spectrum of ALS patients with TBK1 variants and found that the clinical manifestations of TBK1 carriers are diverse. [ABSTRACT FROM AUTHOR] |
|
Copyright of European Journal of Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder