Detection of Genomic Imbalances by Array-Based Comparative Genomic Hybridization in Bulgarian Patients with Autism Spectrum Disorders

ABSTRACT

Autism spectrum disorders (ASDs) constitute a group of behaviorally-defined conditions whose main features are qualitative changes in social interactions, defect in communication abilities, and repetitive and stereotyped interests and activities. ASDs are disorders which can be either isolated, or syndromic. The exact etiology of autism remains unknown, although it is likely to result from a complex combination of genetic and nongenetic factors. One genetic mechanism known to be associated with ASDs is submicroscopic chromosomal imbalances that are undetectable at the level of traditional cytogenetic analysis. Array-based comparative genomic hybridization (array CGH) is a powerful and high-resolution approach for detection of DNA copy number variants (CNVs). Forty-seven autistic patients were investigated using a whole-genome oligo-based array CGH, covering the genome at an average distance of 35 kb. Four clinically significant rearrangements, ranging from 494 kb to 3.47 Mb in size, were identified in 3 patients. Confirmation studies were performed on array CGH results using FISH. These data strongly support the idea that only a whole-genome high-resolution analysis such as array CGH is able to provide an accurate diagnosis for chromosomal imbalance in patients with ASDs.

Keywords:

• array-based comparative genomic hybridization (array CGH)
• autism spectrum disorders (ASDs)
• genomic imbalances