Department of Surgery and Medical-Surgical Specialties, University of Catania, Catania, Italy.
Oasi Research Institute-IRCCS, Troina, Italy.
Neural Plast. 2020 Aug 18;2020:8078103. doi: 10.1155/2020/8078103. eCollection 2020.
The advancements in the next-generation sequencing (NGS) techniques have allowed for rapid, efficient, and cost-time-effective genetic variant detection. However, in both clinical practice and research setting, sequencing is still often limited to the use of gene panels clinically targeted on the genes underlying the disease of interest.
We performed a neurogenetic study through an NGS-based custom sequencing gene panel in order to screen 16 genes in 8 patients with different types of degenerative cognitive disorders (Alzheimer's disease, mild cognitive impairment, frontotemporal dementia, and dementia associated with Parkinson's disease). The study protocol was based on previous evidence showing a high sensitivity and specificity of the technique even when the panel is limited to some hotspot exons.
We found variants of the and genes in three patients; these have been previously identified as pathogenic or likely pathogenic and, therefore, considered "disease causing." In the remaining subjects, the pathogenicity was evaluated according to the guidelines of the American College of Medical Genetics (ACMG). In one patient, the p.R205W variant in the gene was found to be likely pathogenic of the disease. A variant in the and genes found in two patients was classified as benign, whereas the other two (in the and genes) were classified as likely pathogenic according to the ACMG.
Notwithstanding the preliminary value of this study, some rare genetic variants with a probable disease association were detected. Although future application of NGS-based sensors and further replication of these experimental data are needed, this approach seems to offer promising translational perspectives in the diagnosis and management of a wide range of neurodegenerative disorders.
下一代测序（NGS）技术的进步使得快速、高效且具有成本效益的基因变异检测成为可能。然而，在临床实践和研究环境中，测序通常仍然仅限于针对相关疾病的靶基因的临床靶向基因面板。
我们通过基于 NGS 的定制测序基因面板进行了神经遗传学研究，以筛选 8 名患有不同类型退行性认知障碍（阿尔茨海默病、轻度认知障碍、额颞叶痴呆和帕金森病相关痴呆）的患者的 16 个基因。该研究方案基于先前的证据，即使面板仅限于一些热点外显子，该技术也具有很高的灵敏度和特异性。
我们在 3 名患者中发现了 和 基因的变异；这些变异先前已被确定为致病性或可能致病性，因此被认为是“致病的”。在其余受试者中，根据美国医学遗传学学院（ACMG）的指南评估其致病性。在一名患者中， 基因中的 p.R205W 变异被认为可能导致该疾病。在两名患者中发现的 基因和 基因中的变异被归类为良性，而另外两名（在 基因和 基因中）根据 ACMG 归类为可能致病性。
尽管这项研究具有初步价值，但检测到了一些与疾病可能相关的罕见遗传变异。尽管需要进一步应用基于 NGS 的传感器和复制这些实验数据，但这种方法似乎在诊断和管理广泛的神经退行性疾病方面提供了有前景的转化视角。
