Department of Psychiatry, Univeristy of British Columbia, Vancouver, Canada.
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Hum Genet. 2022 May;141(5):1069-1084. doi: 10.1007/s00439-021-02349-1. Epub 2021 Aug 28.
Genetic testing to identify genetic syndromes and copy number variants (CNVs) via whole genome platforms such as chromosome microarray (CMA) or exome sequencing (ES) is routinely performed clinically, and is considered by a variety of organizations and societies to be a "first-tier" test for individuals with developmental delay (DD), intellectual disability (ID), or autism spectrum disorder (ASD). However, in the context of schizophrenia, though CNVs can have a large effect on risk, genetic testing is not typically a part of routine clinical care, and no clinical practice guidelines recommend testing. This raises the question of whether CNV testing should be similarly performed for individuals with schizophrenia. Here we consider this proposition in light of the history of genetic testing for ID/DD and ASD, and through the application of an ethical analysis designed to enable robust, accountable and justifiable decision-making. Using a systematic framework and application of relevant bioethical principles (beneficence, non-maleficence, autonomy, and justice), our examination highlights that while CNV testing for the indication of ID has considerable benefits, there is currently insufficient evidence to suggest that overall, the potential harms are outweighed by the potential benefits of CNV testing for the sole indications of schizophrenia or ASD. However, although the application of CNV tests for children with ASD or schizophrenia without ID/DD is, strictly speaking, off-label use, there may be clinical utility and benefits substantive enough to outweigh the harms. Research is needed to clarify the harms and benefits of testing in pediatric and adult contexts. Given that genetic counseling has demonstrated benefits for schizophrenia, and has the potential to mitigate many of the potential harms from genetic testing, any decisions to implement genetic testing for schizophrenia should involve high-quality evidence-based genetic counseling.
通过全基因组平台（如染色体微阵列 [CMA] 或外显子测序 [ES]）进行基因检测以识别遗传综合征和拷贝数变异（CNV），在临床上通常是常规操作，并且被各种组织和协会认为是发育迟缓（DD）、智力障碍（ID）或自闭症谱系障碍（ASD）患者的“一线”检测方法。然而，在精神分裂症的背景下，尽管 CNV 对风险有很大影响，但基因检测通常不是常规临床护理的一部分，也没有临床实践指南推荐进行检测。这就提出了一个问题，即是否也应该对精神分裂症患者进行 CNV 检测。在这里，我们根据 ID/DD 和 ASD 的基因检测历史，并通过应用旨在实现强大、负责和合理决策的伦理分析来考虑这个提议。使用系统框架和应用相关的生物伦理原则（效益、不伤害、自主性和正义），我们的检查强调，虽然针对 ID 适应症进行 CNV 检测具有相当大的益处，但目前没有足够的证据表明，总体而言，CNV 检测对精神分裂症或 ASD 单一适应症的潜在益处是否超过了潜在危害。然而，尽管严格来说，为没有 ID/DD 的 ASD 或精神分裂症儿童应用 CNV 测试是超适应证使用，但可能存在足够重要的临床实用性和益处，可以超过危害。需要研究来澄清在儿科和成人背景下测试的危害和益处。鉴于遗传咨询已证明对精神分裂症有益，并且有可能减轻遗传检测的许多潜在危害，因此，对精神分裂症进行基因检测的任何决定都应涉及基于高质量证据的遗传咨询。
