Suppr超能文献

年龄对肌萎缩侧索硬化症基因检测决策的影响。

The impact of age on genetic testing decisions in amyotrophic lateral sclerosis.

机构信息

UCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular diseases, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.

Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9RX, UK.

出版信息

Brain. 2022 Dec 19;145(12):4440-4447. doi: 10.1093/brain/awac279.

Abstract

Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative syndrome. In up to 20% of cases, a family history is observed. Although Mendelian disease gene variants are found in apparently sporadic ALS, genetic testing is usually restricted to those with a family history or younger patients with sporadic disease. With the advent of therapies targeting genetic ALS, it is important that everyone treatable is identified. We therefore sought to determine the probability of a clinically actionable ALS genetic test result by age of onset, globally, but using the UK as an exemplar. Blood-derived DNA was sequenced for ALS genes, and the probability of a clinically actionable genetic test result estimated. For a UK subset, age- and sex-specific population incidence rates were used to determine the number of such results missed by restricting testing by age of onset according to UK's National Genomic Test Directory criteria. There were 6274 people with sporadic ALS, 1551 from the UK. The proportion with a clinically actionable genetic test result ranged between 0.21 [95% confidence interval (CI) 0.18-0.25] in the youngest age group to 0.15 (95% CI 0.13-0.17) in the oldest age group for a full gene panel. For the UK, the equivalent proportions were 0.23 (95% CI 0.13-0.33) in the youngest age group to 0.17 (95% CI 0.13-0.21) in the oldest age group. By limiting testing in those without a family history to people with onset below 40 years, 115 of 117 (98% of all, 95% CI 96%-101%) clinically actionable test results were missed. There is a significant probability of a clinically actionable genetic test result in people with apparently sporadic ALS at all ages. Although some countries limit testing by age, doing so results in a significant number of missed pathogenic test results. Age of onset and family history should not be a barrier to genetic testing in ALS.

摘要

肌萎缩侧索硬化症(ALS)是一种异质性神经退行性综合征。在多达 20%的病例中,观察到家族史。尽管在明显的散发性 ALS 中发现了孟德尔疾病基因变异,但基因检测通常仅限于有家族史或年轻的散发性疾病患者。随着针对遗传 ALS 的治疗方法的出现,确定每个可治疗的患者都很重要。因此,我们试图确定全球范围内按发病年龄计算的具有临床可操作性的 ALS 遗传检测结果的概率,但以英国为例。对 ALS 基因进行了血液衍生 DNA 测序,并估计了具有临床可操作性的遗传检测结果的概率。对于英国的一个子集,使用年龄和性别特异性人群发病率来确定根据英国国家基因组测试目录标准按发病年龄限制测试时错过的此类结果的数量。有 6274 名患有散发性 ALS 的人,其中 1551 人来自英国。具有临床可操作性的遗传检测结果的比例在年龄最小的年龄组为 0.21(95%置信区间[CI] 0.18-0.25),在年龄最大的年龄组为 0.15(95% CI 0.13-0.17),用于全基因面板。对于英国,在年龄最小的年龄组中,这一比例为 0.23(95% CI 0.13-0.33),在年龄最大的年龄组中为 0.17(95% CI 0.13-0.21)。通过将无家族史的检测限制在发病年龄低于 40 岁的人群中,117 例(所有病例的 98%,95% CI 96%-101%)具有临床可操作性的检测结果被遗漏。在所有年龄段的明显散发性 ALS 患者中,都有很大概率出现具有临床可操作性的遗传检测结果。尽管有些国家按年龄限制检测,但这样做会导致大量致病检测结果被遗漏。发病年龄和家族史不应成为 ALS 基因检测的障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e4a/9762932/15e10e10e7e4/awac279f1.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验