Hereditary spastic paraplegia (HSP) refers to a group of heterogeneous neurological disorders mainly characterized by corticospinal degeneration (pure forms), but sometimes associated with additional neurological and extrapyramidal features (complex HSP). The advent of next-generation sequencing (NGS) has led to huge improvements in knowledge of HSP genetics and made it possible to clarify the genetic etiology of hundreds of “cold cases,” accelerating the process of reaching a molecular diagnosis. The different NGS-based strategies currently employed as first-tier approaches most commonly involve the use of targeted resequencing panels and exome sequencing, whereas genome sequencing remains a second-tier approach because of its high costs. The question of which approach is the best is still widely debated, and many factors affect the choice. Here, we aim to analyze the diagnostic power of different NGS techniques applied in HSP, by reviewing 38 selected studies in which different strategies were applied in different-sized cohorts of patients with genetically uncharacterized HSP.

遗传性痉挛性截瘫 (HSP) 是指一组异质性神经系统疾病，主要特征为皮质脊髓变性（纯粹形式），但有时伴有其他神经系统和锥体外系特征（复杂 HSP）。新一代测序（NGS）的出现极大地提高了热休克蛋白遗传学知识，使阐明数百个“悬而未决的病例”的遗传病因成为可能，加速了分子诊断的进程。目前用作第一层方法的不同基于 NGS 的策略最常见的是使用靶向重测序面板和外显子组测序，而基因组测序由于成本高昂而仍然是第二层方法。哪种方法最好的问题仍然存在广泛争议，许多因素都会影响选择。在这里，我们旨在通过回顾 38 项选定的研究来分析应用于 HSP 的不同 NGS 技术的诊断能力，其中不同策略应用于不同规模的遗传非特征性 HSP 患者队列。