Mishra Abhishek, Prabha Praisy K, Singla Rubal, Kaur Gurjeet, Sharma Amit Raj, Joshi Rupa, Suroy Benjamin, Medhi Bikash
Dept. of Pharmacology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh 160012, India.
Dept. of Neurology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh 160012, India.
ACS Chem Neurosci. 2022 Jun 15;13(12):1684-1696. doi: 10.1021/acschemneuro.2c00060. Epub 2022 May 28.
Autism spectrum disorders (ASDs) are multifactorial in nature and include both genetic and environmental factors. The increasing evidence advocates an important role of epigenetics in ASD etiology. One of the most common forms of epigenetic changes observed in the case of neurodevelopmental disorders is imprinting which is tightly regulated by developmental and tissue-specific mechanisms. Interestingly, many of these disorders that demonstrate autism-like phenotypes at varying degrees have found involvement of chromosome 15q11-q13 segment. Numerous studies demonstrate occurrence of ASD in the presence of chromosomal abnormalities located mainly in Chr15q11-q13 region. Several plausible candidate genes associated with ASD are in this chromosomal segment, including gamma aminobutyric acid A (GABA) receptor genes and and . The main objective of this review is to highlight the contribution of epigenetic modulations in chromosome 15q11-q13 segment toward the genetic etiology and pathophysiology of ASD. The present review reports the abnormalities in epigenetic regulation on genes and genomic regions located on chromosome 15 in relation to either syndromic (15q11-q13 maternal duplication) or nonsyndromic forms of ASD. Furthermore, studies reviewed in this article demonstrate conditions in which epigenetic dysregulation has been found to be a pathological factor for ASD development, thereby supporting a role for epigenetics in the multifactorial etiologies of ASD. Also, on the basis of the evidence found so far, we strongly emphasize the need to develop future therapeutic strategies as well as screening procedures for ASD that target mechanisms involving genes located on the chromosomal 15q11-q13 segment.
自闭症谱系障碍（ASD）本质上是多因素的，包括遗传和环境因素。越来越多的证据表明表观遗传学在ASD病因学中起着重要作用。在神经发育障碍中观察到的最常见的表观遗传变化形式之一是印记，它受到发育和组织特异性机制的严格调控。有趣的是，许多这些在不同程度上表现出自闭症样表型的疾病都发现与染色体15q11-q13区段有关。大量研究表明，主要位于15号染色体q11-q13区域的染色体异常会导致ASD的发生。与ASD相关的几个可能的候选基因位于这个染色体区段，包括γ-氨基丁酸A（GABA）受体基因等。本综述的主要目的是强调15q11-q13染色体区段的表观遗传调控对ASD遗传病因学和病理生理学的贡献。本综述报告了与综合征性（15q11-q13母系重复）或非综合征性ASD形式相关的位于15号染色体上的基因和基因组区域的表观遗传调控异常。此外，本文综述的研究表明，表观遗传失调已被发现是ASD发展的一个病理因素，从而支持表观遗传学在ASD多因素病因学中的作用。同样，基于目前所发现的证据，我们强烈强调需要针对涉及位于染色体15q11-q13区段的基因的机制，开发未来的ASD治疗策略和筛查程序。
