The genetics of amyotrophic lateral sclerosis

被引：12

作者：

Nijs, Melissa ^{[1
]}

Van Damme, Philip ^{[1
,2
]}

机构：

[1] Univ Leuven, KU Leuven, Leuven Brain Inst, Lab Neurobiol,Dept Neurosci, Leuven, Belgium

[2] Univ Hosp Leuven, Neurol Dept, Herestr 49, B-3000 Leuven, Belgium

来源：

CURRENT OPINION IN NEUROLOGY | 2024年 / 37卷 / 05期

关键词：

C9orf72; gene testing; genotype-phenotype correlation; heritability; SOD1; GENOME-WIDE ASSOCIATION; TARDBP MUTATIONS; HEXANUCLEOTIDE REPEAT; ANALYSES IDENTIFY; ALS; VARIANTS; TDP-43; RISK; ATAXIN-2; JUVENILE;

D O I：

10.1097/WCO.0000000000001294

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Purpose of reviewAmyotrophic lateral sclerosis (ALS) has a strong genetic basis, but the genetic landscape of ALS appears to be complex. The purpose of this article is to review recent developments in the genetics of ALS.Recent findingsLarge-scale genetic studies have uncovered more than 40 genes contributing to ALS susceptibility. Both rare variants with variable effect size and more common variants with small effect size have been identified. The most common ALS genes are C9orf72, SOD1, TARDBP and FUS. Some of the causative genes of ALS are shared with frontotemporal dementia, confirming the molecular link between both diseases. Access to diagnostic gene testing for ALS has to improve, as effective gene silencing therapies for some genetic subtypes of ALS are emerging, but there is no consensus about which genes to test for.SummaryOur knowledge about the genetic basis of ALS has improved and the first effective gene silencing therapies for specific genetic subtypes of ALS are underway. These therapeutic advances underline the need for better access to gene testing for people with ALS. Further research is needed to further map the genetic heterogeneity of ALS and to establish the best strategy for gene testing in a clinical setting.

引用

页码：560 / 569

页数：10

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