Chen Chia-Hsiang, Cheng Min-Chih, Hu Tsung-Ming, Ping Lieh-Yung
Department of Psychiatry, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Department and Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.
Front Genet. 2021 Oct 1;12:620496. doi: 10.3389/fgene.2021.620496. eCollection 2021.
Schizophrenia is a chronic, devastating mental disorder with complex genetic components. Given the advancements in the molecular genetic research of schizophrenia in recent years, there is still a lack of genetic tests that can be used in clinical settings. Chromosomal microarray analysis (CMA) has been used as first-tier genetic testing for congenital abnormalities, developmental delay, and autism spectrum disorders. This study attempted to gain some experience in applying chromosomal microarray analysis as a first-tier genetic test for patients with schizophrenia. We consecutively enrolled patients with schizophrenia spectrum disorder from a clinical setting and conducted genome-wide copy number variation (CNV) analysis using a chromosomal microarray platform. We followed the 2020 "Technical Standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)" to interpret the clinical significance of CNVs detected from patients. We recruited a total of 60 patients (36 females and 24 males) into this study. We detected three pathogenic CNVs and one likely pathogenic CNV in four patients, respectively. The detection rate was 6.7% (4/60, 95% CI: 0.004-0.13), comparable with previous studies in the literature. Also, we detected thirteen CNVs classified as uncertain clinical significance in nine patients. Detecting these CNVs can help establish the molecular genetic diagnosis of schizophrenia patients and provide helpful information for genetic counseling and clinical management. Also, it can increase our understanding of the pathogenesis of schizophrenia. Hence, we suggest CMA is a valuable genetic tool and considered first-tier genetic testing for schizophrenia spectrum disorders in clinical settings.
精神分裂症是一种具有复杂遗传成分的慢性、毁灭性精神障碍。鉴于近年来精神分裂症分子遗传学研究的进展，仍缺乏可用于临床环境的基因检测方法。染色体微阵列分析（CMA）已被用作先天性异常、发育迟缓及自闭症谱系障碍的一线基因检测。本研究试图在将染色体微阵列分析作为精神分裂症患者的一线基因检测应用方面积累一些经验。我们从临床环境中连续纳入精神分裂症谱系障碍患者，并使用染色体微阵列平台进行全基因组拷贝数变异（CNV）分析。我们遵循2020年《结构拷贝数变异解读与报告技术标准：美国医学遗传学与基因组学学会（ACMG）和临床基因组资源（ClinGen）联合共识推荐》来解释从患者中检测到的CNV的临床意义。我们共招募了60名患者（36名女性和24名男性）参与本研究。我们分别在4名患者中检测到3个致病性CNV和1个可能致病性CNV。检出率为6.7%（4/60，95%CI：0.004 - 0.13），与文献中先前的研究相当。此外，我们在9名患者中检测到13个分类为临床意义不明确的CNV。检测这些CNV有助于建立精神分裂症患者的分子遗传学诊断，并为遗传咨询和临床管理提供有用信息。同时，它可以增加我们对精神分裂症发病机制的理解。因此，我们建议CMA是一种有价值的基因工具，可被视为临床环境中精神分裂症谱系障碍的一线基因检测。
