Somatic Mosaicism in Brain Disorders.

IF 28.4 1区医学 Q1 PATHOLOGY

Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-09-03 DOI:10.1146/annurev-pathmechdis-111523-023528

Rachel R Corrigan, Lauren M Mashburn-Warren, Hyojung Yoon, Tracy A Bedrosian

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引用次数: 0

Abstract

Research efforts over the past decade have defined the genetic landscape of somatic variation in the brain. Neurons accumulate somatic mutations from development through aging with potentially profound functional consequences. Recent studies have revealed the contribution of somatic mosaicism to various brain disorders including focal epilepsy, neuropsychiatric disease, and neurodegeneration. One notable finding is that the effect of somatic mosaicism on clinical outcomes can vary depending on contextual factors, such as the developmental origin of a variant or the number and type of cells affected. In this review, we highlight current knowledge regarding the role of somatic mosaicism in brain disorders and how biological context can mediate phenotypes. First, we identify the origins of brain somatic variation throughout the lifespan of an individual. Second, we explore recent discoveries that suggest somatic mosaicism contributes to various brain disorders. Finally, we discuss neuropathological associations of brain mosaicism in different biological contexts and potential clinical utility.

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脑部疾病中的体细胞嵌合。

过去十年的研究工作已经确定了大脑中体细胞变异的遗传情况。神经元从发育到衰老的整个过程中都会积累体细胞变异，并可能产生深远的功能性后果。最近的研究揭示了体细胞突变对各种脑部疾病的影响，包括局灶性癫痫、神经精神疾病和神经变性。一个值得注意的发现是，体细胞嵌合对临床结果的影响会因环境因素而异，如变异的发育起源或受影响细胞的数量和类型。在这篇综述中，我们将重点介绍有关体细胞嵌合在脑部疾病中的作用以及生物背景如何介导表型的现有知识。首先，我们确定了大脑体细胞变异在个体整个生命周期中的起源。其次，我们探讨了最近的一些发现，这些发现表明体细胞嵌合会导致各种脑部疾病。最后，我们讨论了不同生物背景下大脑镶嵌的神经病理学关联以及潜在的临床用途。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annual Review of Pathology-Mechanisms of Disease 医学-病理学

CiteScore

62.60

自引率

0.00%

发文量

期刊介绍： The Annual Review of Pathology: Mechanisms of Disease is a scholarly journal that has been published since 2006. Its primary focus is to provide a comprehensive overview of recent advancements in our knowledge of the causes and development of significant human diseases. The journal places particular emphasis on exploring the current and evolving concepts of disease pathogenesis, as well as the molecular genetic and morphological changes associated with various diseases. Additionally, the journal addresses the clinical significance of these findings. In order to increase accessibility and promote the broad dissemination of research, the current volume of the journal has transitioned from a gated subscription model to an open access format. This change has been made possible through the Annual Reviews' Subscribe to Open program, which allows all articles published in this volume to be freely accessible to readers. As part of this transition, all articles in the journal are published under a Creative Commons Attribution (CC BY) license, which encourages open sharing and use of the research.