Cogan Guillaume, Daida Kensuke, Blauwendraat Cornelis, Billingsley Kimberley, Brice Alexis
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.
National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Center for Alzheimer's and Related Dementias, Bethesda, Maryland, USA.
Mov Disord. 2025 Jun;40(6):996-1008. doi: 10.1002/mds.30151. Epub 2025 Mar 3.
Genetic factors play a central role in neurodegenerative disorders. Over the past few decades, significant progress has been made in identifying the causative genes of numerous monogenic disorders, largely due to the widespread adoption of next-generation sequencing (NGS) technologies in both research and clinical settings. However, many likely monogenic disorders still lack an accurate molecular diagnosis, primarily because conventional NGS methods are not effective at detecting structural variants and repeat expansions, both of which are crucial in many neurogenetic diseases. Recently, long-read sequencing (LRS) and optical genome mapping technologies have emerged as powerful tools, offering the ability to capture more complex genetic variations. These technologies have already led to the discovery of novel genes responsible for well-characterized neurodegenerative diseases (ND), enhancing the understanding of the biological underpinning of these conditions. Although currently LRS is mostly used in a research setting, we anticipate broader implementation of these methods in clinical laboratories in the near future. In this review, we explore the contributions of these technologies to ND research and highlight the remaining challenges for future advancements. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
遗传因素在神经退行性疾病中起着核心作用。在过去几十年里，在确定众多单基因疾病的致病基因方面取得了重大进展，这主要归功于下一代测序（NGS）技术在研究和临床环境中的广泛应用。然而，许多可能的单基因疾病仍然缺乏准确的分子诊断，主要原因是传统的NGS方法在检测结构变异和重复扩增方面效果不佳，而这两者在许多神经遗传疾病中都至关重要。最近，长读长测序（LRS）和光学基因组图谱技术已成为强大的工具，能够捕捉更复杂的基因变异。这些技术已经导致发现了与特征明确的神经退行性疾病（ND）相关的新基因，加深了对这些疾病生物学基础的理解。尽管目前LRS大多用于研究环境，但我们预计在不久的将来这些方法将在临床实验室中得到更广泛的应用。在这篇综述中，我们探讨了这些技术对ND研究的贡献，并强调了未来进展中仍然存在的挑战。© 2025作者。《运动障碍》由Wiley Periodicals LLC代表国际帕金森和运动障碍协会出版。本文由美国政府雇员贡献，在美国其作品属于公共领域。
