Postgraduate Program in Internal Medicine, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, Paraná, Brazil.
Movement Disorders Sector, Neurology Service, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, Paraná, Brazil.
Cerebellum. 2024 Aug;23(4):1552-1565. doi: 10.1007/s12311-023-01629-y. Epub 2023 Nov 11.
Next-generation sequencing (NGS), comprising targeted panels (TP), exome sequencing (ES), and genome sequencing (GS) became robust clinical tools for diagnosing hereditary ataxia (HA). Determining their diagnostic yield (DY) is crucial for optimal clinical decision-making. We conducted a comprehensive systematic literature review on the DY of NGS tests for HA. We searched PubMed and Embase databases for relevant studies between 2016 and 2022 and manually examined reference lists of relevant reviews. Eligible studies described the DY of NGS tests in patients with ataxia as a significant feature. Data from 33 eligible studies showed a median DY of 43% (IQR = 9.5-100%). The median DY for TP and ES was 46% and 41.9%, respectively. Higher DY was associated with specific phenotype selection, such as episodic ataxia at 68.35% and early and late onset of ataxia at 46.4% and 54.4%. Parental consanguinity had a DY of 52.4% (p = 0.009), and the presumed autosomal recessive (AR) inheritance pattern showed 62.5%. There was a difference between the median DY of studies that performed targeted sequencing (tandem repeat expansion, TRE) screening and those that did not (p = 0.047). A weak inverse correlation was found between DY and the extent of previous genetic investigation (rho = - 0.323; p = 0.065). The most common genes were CACNA1A and SACS. DY was higher for presumed AR inheritance pattern, positive family history, and parental consanguinity. ES appears more advantageous due to the inclusion of rare genes that might be excluded in TP.
下一代测序（NGS），包括靶向面板（TP）、外显子组测序（ES）和全基因组测序（GS），已成为诊断遗传性共济失调（HA）的强大临床工具。确定其诊断收益（DY）对于最佳临床决策至关重要。我们对 NGS 测试用于 HA 的 DY 进行了全面的系统文献综述。我们在 2016 年至 2022 年期间在 PubMed 和 Embase 数据库中搜索了相关研究，并手动检查了相关综述的参考文献列表。符合条件的研究描述了 NGS 测试在共济失调患者中的 DY 作为重要特征。来自 33 项符合条件的研究的数据显示，中位 DY 为 43%（IQR=9.5-100%）。TP 和 ES 的中位 DY 分别为 46%和 41.9%。特定表型选择与更高的 DY 相关，例如发作性共济失调为 68.35%，早发性和晚发性共济失调为 46.4%和 54.4%。父母近亲结婚的 DY 为 52.4%（p=0.009），假定常染色体隐性（AR）遗传模式为 62.5%。进行靶向测序（串联重复扩展，TRE）筛查的研究和未进行筛查的研究之间的中位 DY 存在差异（p=0.047）。DY 与先前遗传研究程度之间存在弱负相关（rho=-0.323；p=0.065）。最常见的基因是 CACNA1A 和 SACS。假定 AR 遗传模式、阳性家族史和父母近亲结婚的 DY 更高。由于包括可能在 TP 中排除的罕见基因，ES 似乎更具优势。
