COPY NUMBER VARIATION (CNV) ANALYSIS IN IRANIAN PATIENTS WITH SPORADIC AUTISM USING CYTOGENETIC, MLPA, AND ARRAY-CGH TECHNIQUES

The Autism Spectrum Disorders (ASDs) are common neurodevelopmental disorders estimated to affect 1 in 88 children. ASD is a complex condition, result of genetic, epigenetic and environmental factors. However, Genetic comopnent seems to play an important role. The loss/Gain of 1KB and more nucleotides, Copy number variation (CNV), is the significant genetic factor in the etiology of ASD. The CNV rate is reported as 10-15 in children with ASD. In this study we investigated CNV in 50 Iranian patients with sporadic Autism using High resolution Cytogenetics banding, MLPA, and Array-CGH techniques. All patients had additional features such as Intellectual Disability, Seizure, and Craniofacial anomalies. Two out of 50 (4) patients showed chromosome abnormality including 16p duplication (16p13.11-p13.3) and 15q deletion (15q11.2q13.1). MLPA using both sub-telomeic (p036 and p070) and Autism (p343 and p396) kits was done for 50 patients and CNV was detected in 5 (10) patients both in subtelomeric and interstitial regions, one overlapping the cytogenetic finding. Array CGH was performed for 15 patients most of whom had normal results with the Cytogenetic and MLPA techniques. Six out of 15 (40) patients using array-CGH showed significant CNVs including pathogenic (such as 15q24 Microdeletion), likely pathogenic (such as Xq28 Microdeletion) and Uncertain/ Could be Significant Ones (such as Xp22.33 Microduplication). We performed genotype-phenotype analysis and compared our results with other similar studies. To our knowledge, this is the first study on CNV in Iranian patients with ASD. We strongly recommend the investigation of CNV in patients with Autism with or without additional features. © 2016, Iranian Neurogenetics Society. All rights reserved.