Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.
Schulich School of Medicine and Dentistry, Western University, London, Canada.
Amyotroph Lateral Scler Frontotemporal Degener. 2023 Aug;24(5-6):420-435. doi: 10.1080/21678421.2023.2173015. Epub 2023 Mar 10.
: In 2021, the Clinical Genome Resource (ClinGen) amyotrophic lateral sclerosis (ALS) spectrum disorders Gene Curation Expert Panel (GCEP) was established to evaluate the strength of evidence for genes previously reported to be associated with ALS. Through this endeavor, we will provide standardized guidance to laboratories on which genes should be included in clinical genetic testing panels for ALS. In this manuscript, we aimed to assess the heterogeneity in the current global landscape of clinical genetic testing for ALS. : We reviewed the National Institutes of Health (NIH) Genetic Testing Registry (GTR) and members of the ALS GCEP to source frequently used testing panels and compare the genes included on the tests. : 14 clinical panels specific to ALS from 14 laboratories covered 4 to 54 genes. All panels report on , , , and ; 50% included or offered the option of including hexanucleotide repeat expansion (HRE) analysis. Of the 91 genes included in at least one of the panels, 40 (44.0%) were included on only a single panel. We could not find a direct link to ALS in the literature for 14 (15.4%) included genes. : The variability across the surveyed clinical genetic panels is concerning due to the possibility of reduced diagnostic yields in clinical practice and risk of a missed diagnoses for patients. Our results highlight the necessity for consensus regarding the appropriateness of gene inclusions in clinical genetic ALS tests to improve its application for patients living with ALS and their families.
2021 年，临床基因组资源（ClinGen）肌萎缩侧索硬化症（ALS）谱障碍基因养护专家小组（GCEP）成立，旨在评估先前报道与 ALS 相关的基因的证据强度。通过这项努力，我们将为实验室提供标准化的指导，确定哪些基因应包含在 ALS 的临床遗传测试面板中。在本文中，我们旨在评估目前全球 ALS 临床遗传测试的异质性。我们审查了美国国立卫生研究院（NIH）遗传测试登记处（GTR）和 ALS GCEP 的成员，以获取常用的测试面板，并比较测试中包含的基因。来自 14 个实验室的 14 个专门针对 ALS 的临床面板涵盖了 4 到 54 个基因。所有的面板都报告了、、、和；50%的面板包括或提供 hexanucleotide repeat expansion (HRE) 分析的选项。在至少一个面板中包含的 91 个基因中，有 40 个（44.0%）仅包含在一个单一的面板中。我们在文献中无法为包含在基因中 14 个（15.4%）找到与 ALS 直接相关的基因。由于在临床实践中诊断产量降低的可能性以及对患者漏诊的风险，调查的临床遗传面板之间的这种变异性令人担忧。我们的研究结果强调了在临床遗传 ALS 测试中适当纳入基因方面达成共识的必要性，以改善其在与 ALS 患者及其家属的应用。
