Detecting the NOTCH2NLC Repeat Expansion in Neuronal Intranuclear Inclusion Disease
Detecting the NOTCH2NLC Repeat Expansion in Neuronal Intranuclear Inclusion Disease
复制标题
检测神经元核内包涵体病中的 NOTCH2NLC 重复扩增
DOI：
10.1007/978-1-0716-2357-2_7
复制
发表时间：
2022
期刊：
影响因子：
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通讯作者：
N. Matsumoto
中科院分区：
文献类型：
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作者：
S. Mitsuhashi;A. Fujita;N. Matsumoto
神经元核内包涵体病(NIID，OMIM#：603472)是一种以多种神经系统症状为特征的神经退行性疾病，包括认知障碍、共济失调和神经病。在组织病理学上，NIID的特征是在神经元和神经胶质细胞以及其他细胞类型(如皮肤成纤维细胞)中发现泛素阳性的嗜酸性透明质核内包涵体。NOTCH2NLC基因5‘外显子GGC三联体重复扩增导致家族性和散发性NIID。在本章中，我们描述了我们最初开发的两种基因诊断方法，用于识别NIID患者的致病重复扩增：重复启动聚合酶链式反应(Repeat-Primed PCR)和长读测序。重复启动的聚合酶链式反应能够对大量患者进行检测，而且更具成本效益，适合在临床环境中进行快速筛查。长阅读测序方法可以通过焦点分析和全基因组分析来识别这些重复扩增，并表征其精确的重复结构。
Neuronal intranuclear inclusion disease (NIID, OMIM#:603472) is a neurodegenerative disease characterized by a variety of neurological symptoms, including cognitive impairment, ataxia, and neuropathy. Histopathologically, NIID is characterized by ubiquitin-positive eosinophilic hyaline intranuclear inclusions found in neurons and glial cells, in addition to other cell types, such as skin fibroblasts. GGC triplet repeat expansions in the 5′ exons ofNOTCH2NLCcause NIID in both familial and sporadic cases. In this chapter, we describe two genetic diagnosis methods that we originally developed to identify the disease-causing repeat expansions in NIID patients: repeat-primed PCR and long-read sequencing. Repeat-primed PCR enables the testing of a large number of patients and is more cost-effective and suitable for the rapid screening performed in clinical settings. The long-read sequencing approach can identify these repeat expansions through focal and genome-wide analyses and characterize their precise repeat structures.