目的: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,和患者的需求推动了ALS基因检测的使用增加。尽管取得了这些进展,向ALS患者提供基因检测还不是“护理标准”。“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的遗传咨询和检测实践,遗传咨询师或任何照顾ALS患者的提供者。
方法:确定核心临床问题,并根据系统评价和荟萃分析(PRISMA-P)2015方法的首选报告项目进行快速评价。起草了准则建议,并通过结合两个系统评估了每项建议的证据强度:评估,开发和评估(等级)系统以及在实践和预防中的基因组应用评估(EGAPP)。使用改进的Delphi方法在一组内容专家之间就每个指南声明达成共识。
结果:共制定了35个指南声明。总之,所有患有ALS的人都应该接受单步基因检测,由C9orf72分析组成,随着SOD1,FUS,还有TARDBP,至少。描述了在测试之前和之后应提供的关键教育和遗传风险评估。为商业实验室提供有关C9orf72和其他基因的测试方法和报告的具体指导。
结论: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导航基因检测的好处和挑战。
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.