Abstract
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.
Highlights
Schizophrenia is a chronic debilitating mental disorder marked by delusions, hallucinations, erratic emotions, bizarre behaviors, and cognitive deficits
We previously reported three novel rare copy number variation (CNV) associated with schizophrenia in three families, respectively (Liao et al, 2012), indicating the potential clinical utility of chromosomal microarray as a genetic test for schizophrenia in our population
Chromosomal microarray analysis (CMA) has been used as a first-tier genetic test in patients with intellectual disability, congenital abnormalities, and autism spectrum disorders (Miller et al, 2010), and several studies suggested the clinical utility of CMA for schizophrenia and other psychiatric disorders (Costain et al, 2013; Baker et al, 2014; Lowther et al, 2017a; Lowther et al, 2017b)
Summary
Schizophrenia is a chronic debilitating mental disorder marked by delusions, hallucinations, erratic emotions, bizarre behaviors, and cognitive deficits. 1% of the general population is affected by the disease. It is a complex disorder involving genetic and environmental factors, and genetic factors play a significant role in the genesis of schizophrenia. Copy number variations (CNVs) are deleted and duplicated genomic DNA segments resulting from aberrant chromosomal rearrangement. They are associated with human health and diseases (Harel and Lupski, 2018; Hu et al, 2018). Accumulating evidence indicates that rare CNVs contribute significantly to the genetic basis of neuropsychiatric disorders, such as intellectual disability, autism spectrums disorder (ASD), and schizophrenia (Rutkowski et al, 2017; Lowther et al, 2017a). Identifying disease-associated CNVs can help establish cell and animal models of neuropsychiatric disorders to elucidate the pathogenesis and facilitate new therapeutic regimens (Nomura and Takumi, 2012; Flaherty and Brennand, 2017; Rutkowski et al, 2017; Takumi and Tamada, 2018)
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