A copy number variation morbidity map ofdevelopmental delay

To understand the genetic heterogeneity underlying developmental delay, we compared copy number variants (CNVs) in 15,767
children with intellectual disability and various congenital defects (cases) to CNVs in 8,329 unaffected adult controls. We
estimate that ~14.2% of disease in these children is caused by CNVs >400 kb. We observed a greater enrichment of CNVs in
individuals with craniofacial anomalies and cardiovascular defects compared to those with epilepsy or autism. We identified 59
pathogenic CNVs, including 14 new or previously weakly supported candidates, refined the critical interval for several genomic
disorders, such as the 17q21.31 microdeletion syndrome, and identified 940 candidate dosage-sensitive genes. We also
developed methods to opportunistically discover small, disruptive CNVs within the large and growing diagnostic array datasets.
This evolving CNV morbidity map, combined with exome and genome sequencing, will be critical for deciphering the genetic
basis of developmental delay, intellectual disability and autism spectrum disorders.