The emergence of microarray technologies that can detect sub-microscopic structural variation revealed extensive copy number variation (CNV) across the human genome (23-26) and provided new opportunities for genome-wide assessment of rare variation. Studies in schizophrenia (SCZ) (27-33) and ASD (34-37) demonstrated an over-representation of rare CNVs, particularly genic de novo variants (30, 34, 35, 38), and highlighted molecular mechanisms that likely play a role in these conditions. Moreover, recent replicated findings show that more than one developmental neuropsychiatric disorder may share the same rare variant as a risk factor. For example, evidence implicating structural variants at the regions 16p11.2 (33, 39), 22q11.2 (40, 41), 1q21 (27, 32, 42-44), and the genes Neurexin 1 (NRXN1) (34, 36, 37, 45, 46) and SH3 and multiple ankyrin repeat domains 3 (SHANK3) (47) in both SCZ and ASD support the hypothesis of shared biological pathways in these conditions. Similarly, the single genome-wide copy number variation study published to date in TS identified rare variants at the NRXN1 and catenin, alpha 3 (CTNNA3) loci, leading the authors to hypothesize an overlap of risk with both ASD and SCZ (48).
