期刊
JOURNAL OF NEUROLOGY
卷 268, 期 10, 页码 3766-3776出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00415-021-10521-w
关键词
Amyotrophic lateral sclerosis; Frontotemporal degeneration; Next generation sequencing; Genetic heterogeneity; Mutation screening
资金
- Alma Mater Studiorum Universita di Bologna within the CRUI-CARE Agreement
Research suggests that genetic abnormalities in major ALS genes primarily affect patients with a family history of pure ALS, while rare ALS/FTD gene variants are more common in patients with a family history of other neurodegenerative diseases. These two genetic components may help guide genetic screening protocols.
Background 5-10% of amyotrophic lateral sclerosis (ALS) patients presented a positive family history (fALS). More than 30 genes have been identified in association with ALS/frontotemporal dementia (FTD) spectrum, with four major genes accounting for 60-70% of fALS. In this paper, we aimed to assess the contribution to the pathogenesis of major and rare ALS/FTD genes in ALS patients. Methods We analyzed ALS and ALS/FTD associated genes by direct sequencing or next-generation sequencing multigene panels in ALS patients. Results Genetic abnormalities in ALS major genes included repeated expansions of hexanucleotide in C9orf72 gene (7.3%), mutations in SOD1 (4.9%), FUS (2.1%), and TARDBP (2.4%), whereas variants in rare ALS/FTD genes affected 15.5% of subjects overall, most frequently involving SQSTM1 (3.4%), and CHMP2B (1.9%). We found clustering of variants in ALS major genes in patients with a family history for pure ALS, while ALS/FTD related genes mainly occurred in patients with a family history for other neurodegenerative diseases (dementia and/or parkinsonism). Conclusions Our data support the presence of two different genetic components underlying ALS pathogenesis, related to the presence of a family history for ALS or other neurodegenerative diseases. Thus, family history may help in optimizing the genetic screening protocol to be applied.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据