Department of Neurology, Peking Union Medical College and Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, 100730, China.
Neurol Sci. 2024 Apr;45(4):1515-1522. doi: 10.1007/s10072-023-07178-w. Epub 2023 Nov 11.
This study is to determine the incidence of genetic forms of amyotrophic lateral sclerosis (ALS) in clinic-based population.
Next-generation sequencing (NGS) of whole exome sequencing (WES) was conducted among a total of 374 patients with definite or probable ALS to identify ALS-associated genes based on ALSoD database ( https://alsod.ac.uk ) [2023-07-01].
Variants of ALS-associated genes were detected in 54.01% (202/374) ALS patients, among which 8.29% (31/374) were pathogenic/likely pathogenic (P/LP). The detection rates of P/LP variants were significantly higher in familial ALS than sporadic ALS (42.31% vs 5.75%, p < 0.001), while VUS mutations were more commonly detected in sporadic ALS (23.07% vs 47.13%, p = 0.018). There is no significant difference in detection rate between patients with and without early onset (8.93% vs 7.77%), rapid progression (9.30% vs 8.91%), cognitive decline (15.00% vs 7.93%), and cerebellar ataxia (20.00% vs 8.15%) (p > 0.05).
Over half of our ALS patients carried variants of ALS-related genes, most of which were variants of uncertain significance (VUS). Family history of ALS could work as strong evidence for carrying P/LP variants regarding ALS. There was no additionally suggestive effect of indicators including early onset, progression rate, cognitive decline, or cerebellar ataxia on the recommendation of genetic testing in clinical practice.
本研究旨在确定基于临床人群的肌萎缩侧索硬化症（ALS）遗传形式的发病率。
对总共 374 例明确或可能的 ALS 患者进行全外显子组测序（WES）的下一代测序（NGS），以根据 ALSoD 数据库（https://alsod.ac.uk）[2023-07-01]确定 ALS 相关基因。
在 54.01%（202/374）的 ALS 患者中检测到 ALS 相关基因的变异，其中 8.29%（31/374）为致病性/可能致病性（P/LP）。家族性 ALS 患者的 P/LP 变异检出率明显高于散发性 ALS（42.31% vs 5.75%，p<0.001），而散发性 ALS 中更常见的是意义未明的变异（VUS）突变（23.07% vs 47.13%，p=0.018）。在发病年龄早（8.93% vs 7.77%）、进展迅速（9.30% vs 8.91%）、认知下降（15.00% vs 7.93%）和小脑共济失调（20.00% vs 8.15%）的患者之间，检测率无显著差异（p>0.05）。
超过一半的 ALS 患者携带 ALS 相关基因的变异，其中大多数为意义未明的变异（VUS）。ALS 的家族史可作为携带 P/LP 变异的有力证据。在临床实践中，发病年龄早、进展速度、认知下降或小脑共济失调等指标对遗传检测的推荐没有额外的提示作用。
