Molecular Genetics, Genomics, Mechanisms of Diseases
AB051. Chromosomal microarray analysis in a large cohort of Thai patients with autism spectrum disorder
Juthamas Worachotekamjorn1, Tippawan Hansakunachai2, Kitiwan Rojnueangnit2, Rawiwan Roongpraiwan3, Nichara Ruangdaraganon3, Duangrurdee Wattanasirichaigoon3, Natini Jinawath4, Pornprot Limprasert5
1Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand; 2Department of Pediatrics, Faculty of Medicine, Thammasat University, Pathumthani, Thailand;3Department of Pediatrics, Ramathibodi Hospital, 4Research Center, Ramathibodi Hospital, Faculty of Medicine, Mahidol University, Bangkok, Thailand;5Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
Background: Chromosomal microarray (CMA) is now recommended as the first-tier clinical diagnostic test for detecting copy number variations (CNVs) in patients with autism spectrum disorder (ASD) of unknown cause. The aim of this study was to identify ASD associated-CNVs in a large cohort of Thai patients with ASD using CMA.
Methods: CMA was performed in 130 normal-karyotype Thai patients with ASD, and negative results from Fragile X and MECP2 DNA tests using the Illumina HumanCytoSNP-12 v2.1 array (n=16 cases) and the Illumina CytoSNP-850K BeadChip (n=114 cases).
Results: We identified 8 (6.1%) pathogenic CNVs and 7 (5.4%) variants of unknown clinical significance (VOUS) with likely pathogenic CNVs. The overall diagnostic yield of abnormal CNVs in the Thai ASD patients was 11.5% (15/130), which is comparable to the reported yield in studies in other populations. Among the pathogenic CNVs, there were 7 patients with well-known microduplication or microdeletion syndromes (i.e., 1q21.1 duplication, 15q13.3 microdeletion and16p13.11 microduplication syndrome). In addition, CMA also revealed uniparental disomy (UPD) of chromosome 15 in one case. Methylation-specific polymerase chain reaction (MS-PCR) and haplotype analysis were then performed on this patient, confirming that he had Angelman syndrome with autistic features caused by paternal UPD of chromosome 15. Interestingly, we identified a new and de novo 1p35.2 duplication encompassing SERINC2 gene that are highly expressed in the brain but have not yet been implicated in ASD.
Conclusions: This study is the first CMA testing in a large cohort of Thai patients with ASD. Our findings support the usefulness of CMA as a diagnostic test in patients with ASD of unknown cause. In addition, we propose considering the SERINC2 gene as a potential novel ASD candidate gene that warrants further investigation.
Keywords: autism spectrum disorder (ASD); autism; copy number variation (CNV); microarray; Thailand
doi: 10.21037/atm.2017.s051
Cite this article as: Worachotekamjorn J, Hansakunachai T, Rojnueangnit K, Roongpraiwan R, Ruangdaraganon N, Wattanasirichaigoon D, Jinawath N, Limprasert P. Chromosomal microarray analysis in a large cohort of Thai patients with autism spectrum disorder. Ann Transl Med 2017;5(Suppl 2):AB051. doi: 10.21037/atm.2017.s051
