Investigation of Copy Number Variation by arrayCGH in Turkish Children and Adolescents Diagnosed with Autism Spectrum Disorders

Abstract

The development of whole-genome screening methodologies for the detection of copy number variations (CNVs), such as array-based comparative genomic hybridization (aCHG), provides a much higher resolution than karyotyping leading to the identification of novel microdeletion and microduplication syndromes often associated with an autism spectrum disease (ASD) phenotype. The aim of the study was to determine CNVs of patients with ASD by using array-based comparative genomic hybridization.Methods: Fifty-three patients diagnosed with ASD between 20.01.2014 and 14.01.2015 were included in the study. Chromosome analysis of the patients was performed from peripheral blood cultures and analysed as normal. All patients were evaluated with P064C1 and P096A2 MLPA probes in terms of 16 mental retardation related syndromes. For aCGH method, SurePrint G3 Human microarrays 8x60K were used with genomic DNA isolated from peripheral blood.Results: According to results of 53 patients who were included in and performed with arrayCGH, 8 (15%) patients had CNVs classified as pathogenic or variant of unknown significance (VOUS) in the study. We detected a pathogenic NRXN1 gene partial CNV deletion (2p16.3) in two patients. Also we identified a 900 kb duplication of 4p15.31 including SLIT2 gene, and a 245 kb duplication of 15q11.2 including PWRN1 gene in one patient. Our other findings are considered to be a variant of unknown significance (VOUS). Conclusion:The results of the study support the literature knowledge, where the copy number variations that cannot be detected with conventional cytogenetics methods in terms of size may happen in patients with ASD.

Depression-/Anxiety-Like Behavior Alterations in Adult Slit2 Transgenic Mice

“…Thus, abnormalities in the Slit/Robo pathway are observed in these neuropsychiatric disorders. There is increasing evidence that suggest Slit2 is associated with some neuropsychiatric disorders, including MDD (Huls et al, 2020), AD (Li et al, 2015), Parkinson's disease (PD) (Lin and Isacson, 2006), TLE (Fang et al, 2010), and ASD (Perez et al, 2016;Gorker et al, 2018). Depression and anxiety are common psychiatric disorders, and their pathogenesis is not well-understood.…”

“…Slit/Robo signaling also mediates other biological processes such as angiogenesis, leukocyte chemotaxis, cell proliferation, and tumor growth and progression (Borrell et al, 2012;Yuen and Robinson, 2013;Jiang et al, 2019). Increasing evidence suggests that disturbance in Slit/Robo signaling plays a role in several neuropsychiatric disorders, including Alzheimer's disease (AD), autism spectrum disorder (ASD), temporal lobe epilepsy (TLE), and major depressive disorder (MDD) (Fang et al, 2010;Li et al, 2015;Gorker et al, 2018;Bai et al, 2020). Bai et al found that the Slit2 protein could be a novel biomarker candidate through proteomics profiling of the cerebrospinal fluid (CSF) in patients with AD (Bai et al, 2020).…”

The Role of Copy Number Variations and FHIT Gene on Phenotypic Characteristics of Cases Diagnosed with Autism Spectrum Disorder

“…This was the first report, in which molecular karyotyping techniques were successfully applied in ASD patients from Turkey. In the second study presenting CNVs of patients with ASD, a larger sample size was analyzed [Gorker et al, 2018]. A total of 53 patients were evaluated using array-CGH, and 8 (15%) patients had pathogenic CNVs or VUS (2 pathogenic and 7 VUS).…”