Copy Number Variation (CNV) analysis and Next generation Sequencing (NGS), in some Iranian Patients with Autism

The autism spectrum disorders (ASDs) are common neurodevelopmental and heterogeneous disorders estimated to affect 1 in 68 children. Genetics plays an important role in its etiology. Copy number variations account for 10-15% in sporadic ASD cases. Next generation sequencing (NGS) is a valuable technique in identifying causative mutations. Materials and Methods We used karyotyping, MLPA (Subtelomeric and Autism kits) and array CGH to detect CNVs in 50 Iranian patients with sporadic non syndromic autism with additional clinical features including intellectual disability, seizure, and craniofacial anomalies. We have also recruited 15 familial non syndromic ASD cases, and have used SNP Array and Whole Exome Sequencing. Results In the sporadic cases, two 0f 50 (4%) patients showed chromosome abnormality including 16p duplication (16p13.11-p13.3) and 15q deletion (15q11.2q13.1). MLPA detected CNVs in 5 patients (10%) both in subtelomeric and interstitial regions. Array CGH was performed for 15 patients. Six out of 15 patients (40%) showed significant CNVs including two pathogenic losses (15q24 and Xq28 microdeletions), and 4 likely pathogenic gains (15q13.3, 7q36.3, Xp22.33 and 10q21.2-21.3 microduplications).In the familial cases, SNP array for homozygous regions, Whole Exome Sequencing (WES) and co segregation analysis are carried out. Conclusion We recommend testing patients with non-familial autism and additional features for CNVs. The NGS analysis for familial ASD patients where monogenic inheritance is indicated, in particular in extended families with affected branch members, can be of great value in identifying the causative mutation in the family.

کلیدواژه ها:

Autism Spectrum Disorder ، CNV ، Karyotype ، MLPA ، Array-CGH ، NGS