IntellxxDNA, Austin, TX 78731, USA.
LaValley MD Protocols, Austin, TX 78759, USA.
Int J Mol Sci. 2022 Feb 16;23(4):2167. doi: 10.3390/ijms23042167.
Molecular biology combined with genomics can be a powerful tool for developing potential intervention strategies for improving outcomes in children with autism spectrum disorders (ASD). Monogenic etiologies rarely cause autism. Instead, ASD is more frequently due to many polygenic contributing factors interacting with each other, combined with the epigenetic effects of diet, lifestyle, and environment. One limitation of genomics has been identifying ways of responding to each identified gene variant to translate the information to something clinically useful. This paper will illustrate how understanding the function of a gene and the effects of a reported variant on a molecular level can be used to develop actionable and targeted potential interventions for a gene variant or combinations of variants. For illustrative purposes, this communication highlights a specific genomic variant, SHANK3. The steps involved in developing molecularly genomically targeted actionable interventions will be demonstrated. Cases will be shared to support the efficacy of this strategy and to show how clinicians utilized these targeted interventions to improve ASD-related symptoms significantly. The presented approach demonstrates the utility of genomics as a part of clinical decision-making.
分子生物学与基因组学相结合,可以成为开发潜在干预策略的有力工具,以改善自闭症谱系障碍(ASD)儿童的治疗效果。单基因病因很少导致自闭症。相反,ASD 更常由许多多基因的相互作用的贡献因素引起,加上饮食、生活方式和环境的表观遗传效应。基因组学的一个局限性在于,如何识别针对每个已识别基因变异的反应方式,将信息转化为具有临床实用性的东西。本文将举例说明如何理解基因的功能以及报道的变异在分子水平上对基因变异或变异组合的影响,从而开发针对该基因变异或变异组合的可行的靶向潜在干预措施。为了说明问题,本交流重点介绍了一个特定的基因组变异,即 SHANK3。将展示开发针对分子遗传学的可操作的靶向干预措施的步骤。将分享案例以支持该策略的有效性,并展示临床医生如何利用这些靶向干预措施显著改善与 ASD 相关的症状。所提出的方法展示了基因组学作为临床决策的一部分的实用性。