a Department of Clinical Medicine, Faculty of Medicine and Health Sciences , Macquarie University , Sydney , Australia.
b Centre for MND Research, Department of Biomedical Science, Faculty of Medicine and Health Sciences , Macquarie University , Sydney , Australia.
Amyotroph Lateral Scler Frontotemporal Degener. 2019 Aug;20(5-6):310-316. doi: 10.1080/21678421.2019.1588904. Epub 2019 Mar 23.
hexanucleotide repeat expansions are the most common known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Genetic testing for expansions in patients with ALS and/or FTD and their relatives has become increasingly available since hexanucleotide repeat expansions were first reported in 2011. The repeat number is highly variable and the threshold at which repeat size leads to neurodegeneration remains unknown. We present the case of an ALS patient who underwent genetic testing through our Motor Neurone Disease Clinic. We highlight current limitations to analysing and interpreting expansion test results and describe how this resulted in discordant reports of pathogenicity between testing laboratories that confounded the genetic counselling process. We conclude that patients with ALS or FTD and their at-risk family members, need to be adequately counselled about the limitations of current knowledge to ensure they are making informed decisions about genetic testing for . Greater collaboration between clinicians, testing laboratories and researchers is required to ensure risks to patients and their families are minimised.
六核苷酸重复扩展是肌萎缩侧索硬化症 (ALS) 和额颞叶痴呆 (FTD) 最常见的已知病因。自 2011 年首次报道六核苷酸重复扩展以来，对 ALS 和/或 FTD 患者及其亲属进行扩展基因检测的方法越来越多。重复数量高度可变，导致神经退行性变的重复大小阈值仍不清楚。我们介绍了一位在我们的运动神经元疾病诊所接受基因检测的 ALS 患者的病例。我们强调了目前分析和解释 扩展测试结果的局限性，并描述了这如何导致检测实验室之间致病性的报告不一致，从而使遗传咨询过程变得复杂。我们的结论是，ALS 或 FTD 患者及其有风险的家庭成员需要充分了解当前知识的局限性，以确保他们就 基因检测做出明智的决定。需要加强临床医生、检测实验室和研究人员之间的合作，以确保将患者及其家属的风险降至最低。
