La Cognata Valentina, Cavallaro Sebastiano
Institute for Biomedical Research and Innovation, National Research Council, 95126 Catania, Italy.
Biomedicines. 2022 Jul 29;10(8):1836. doi: 10.3390/biomedicines10081836.
Lysosomal storage diseases (LSDs) are a heterogeneous group of rare multisystem metabolic disorders occurring mostly in infancy and childhood, characterized by a gradual accumulation of non-degraded substrates inside the cells. Although biochemical enzymatic assays are considered the gold standard for diagnosis of symptomatic patients, genotyping is a requirement for inclusion in enzyme replacement programs and is a prerequisite for carrier tests in relatives and DNA-based prenatal diagnosis. The emerging next-generation sequencing (NGS) technologies are now offering a powerful diagnostic tool for genotyping LSDs patients by providing faster, cheaper, and higher-resolution testing options, and are allowing to unravel, in a single integrated workflow SNVs, small insertions and deletions (indels), as well as major structural variations (SVs) responsible for the pathology. Here, we summarize the current knowledge about the most recurrent and private SVs involving LSDs-related genes, review advantages and drawbacks related to the use of the NGS in the SVs detection, and discuss the challenges to bring this type of analysis in clinical diagnostics.
溶酶体贮积症（LSDs）是一组异质性的罕见多系统代谢紊乱疾病，大多发生于婴幼儿期，其特征是细胞内未降解底物逐渐蓄积。尽管生化酶学检测被认为是有症状患者诊断的金标准，但基因分型是纳入酶替代治疗项目的必要条件，也是亲属携带者检测和基于DNA的产前诊断的先决条件。新兴的下一代测序（NGS）技术现在为LSDs患者的基因分型提供了一种强大的诊断工具，通过提供更快、更便宜和更高分辨率的检测选项，并允许在单个整合工作流程中解析导致病变的单核苷酸变异（SNV）、小插入和缺失（indel）以及主要结构变异（SV）。在此，我们总结了目前关于涉及LSDs相关基因的最常见和罕见SV的知识，回顾了在SV检测中使用NGS的优缺点，并讨论了将此类分析引入临床诊断的挑战。
