Division of Human Genetics, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Ann Clin Transl Neurol. 2023 Nov;10(11):2074-2091. doi: 10.1002/acn3.51895. Epub 2023 Sep 10.
Advances in amyotrophic lateral sclerosis (ALS) gene discovery, ongoing gene therapy trials, and patient demand have driven increased use of ALS genetic testing. Despite this progress, the offer of genetic testing to persons with ALS is not yet "standard of care." Our primary goal is to develop clinical ALS genetic counseling and testing guidelines to improve and standardize genetic counseling and testing practice among neurologists, genetic counselors or any provider caring for persons with ALS.
Core clinical questions were identified and a rapid review performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-P) 2015 method. Guideline recommendations were drafted and the strength of evidence for each recommendation was assessed by combining two systems: the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) System and the Evaluation of Genomic Applications in Practice and Prevention (EGAPP). A modified Delphi approach was used to reach consensus among a group of content experts for each guideline statement.
A total of 35 guideline statements were developed. In summary, all persons with ALS should be offered single-step genetic testing, consisting of a C9orf72 assay, along with sequencing of SOD1, FUS, and TARDBP, at a minimum. The key education and genetic risk assessments that should be provided before and after testing are delineated. Specific guidance regarding testing methods and reporting for C9orf72 and other genes is provided for commercial laboratories.
These evidence-based, consensus guidelines will support all stakeholders in the ALS community in navigating benefits and challenges of genetic testing.
肌萎缩侧索硬化症 (ALS) 基因发现的进展、正在进行的基因治疗试验以及患者的需求推动了对 ALS 基因检测的更多使用。尽管取得了这些进展，但 ALS 患者的基因检测提供仍未“成为标准护理”。我们的主要目标是制定临床 ALS 遗传咨询和检测指南，以改善和规范神经科医生、遗传咨询师或任何照顾 ALS 患者的提供者的遗传咨询和检测实践。
根据系统评价和荟萃分析的首选报告项目 (PRISMA-P) 2015 方法确定核心临床问题并进行快速审查。起草指南建议，并通过结合两种系统来评估每个建议的证据强度：推荐评估、制定和评估 (GRADE) 系统和实践和预防中的基因组应用评估 (EGAPP)。采用改良 Delphi 方法，就每个指南声明在一组内容专家中达成共识。
共制定了 35 条指南声明。总之，应向所有 ALS 患者提供单步基因检测，最低限度应包括 C9orf72 检测，以及 SOD1、FUS 和 TARDBP 的测序。阐述了在检测前后应提供的关键教育和遗传风险评估。为商业实验室提供了有关 C9orf72 和其他基因的测试方法和报告的具体指导。
这些基于证据的共识指南将支持 ALS 社区的所有利益相关者在基因检测的获益和挑战方面进行导航。
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