Abstract
Copy number variants (CNVs) have repeatedly been found to cause or predispose to autism spectrum disorders (ASDs). For diagnostic purposes, we screened 194 individuals with ASDs for CNVs using Illumina SNP arrays. In several probands, we also analyzed candidate genes located in inherited deletions to unmask autosomal recessive variants. Three CNVs, a de novo triplication of chromosome 15q11–q12 of paternal origin, a deletion on chromosome 9p24 and a de novo 3q29 deletion, were identified as the cause of the disorder in one individual each. An autosomal recessive cause was considered possible in two patients: a homozygous 1p31.1 deletion encompassing PTGER3 and a deletion of the entire DOCK10 gene associated with a rare hemizygous missense variant. We also identified multiple private or recurrent CNVs, the majority of which were inherited from asymptomatic parents. Although highly penetrant CNVs or variants inherited in an autosomal recessive manner were detected in rare cases, our results mainly support the hypothesis that most CNVs contribute to ASDs in association with other CNVs or point variants located elsewhere in the genome. Identification of these genetic interactions in individuals with ASDs constitutes a formidable challenge.
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Acknowledgements
We thank the P3S platform, the ‘Plateau technique Mutualisé du GHU Est’, and the genotyping and sequencing platform of the ICM for technical assistance and the DNA and cell bank of CRICM for DNA extraction and cell culture. We also thank Dr Merle Ruberg for critical reading of the manuscript and Sophie Rivaud-Pechoux for her help with the statistical analysis. This study was financially supported by AP-HP (DHOS), Fondation de France, ERA-NET NEURON EUHFAUTISM and INSERM.
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Nava, C., Keren, B., Mignot, C. et al. Prospective diagnostic analysis of copy number variants using SNP microarrays in individuals with autism spectrum disorders. Eur J Hum Genet 22, 71–78 (2014). https://doi.org/10.1038/ejhg.2013.88
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DOI: https://doi.org/10.1038/ejhg.2013.88
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