Further, the same genes in humans may not have the same regulatory pathways and expression patterns as that occurring in the brains of non-humans. Some animal studies showing statistical differences between wild-type and homozygous knockout mice fail to demonstrate comparable differences when using heterozygous mice, the genetic state most applicable to WS. Further, the scarcity of AWSdel cases have resulted in only one or two cases described in each report. These factors have made it difficult to attribute specific cognitive functions to particular sets of genes. Our study attempted to overcome some of these limitations by examining eight individuals with three types of varying atypical deletions, while also assessing brain structure for the first time in AWSdel cases. A major limitation is that our current level of analysis only allows attribution of subsets of genes to neuroanatomical and cognitive findings. It is likely that there is more than one contributory gene, gene-gene interactions within and outside the WS deletion, as well as environmental influences and stochastic processes that could contribute to neuroanatomical variations. Another limitation is that, similar to typical controls, individuals with WS demonstrate inter-individual differences in neuropsychological and behavioral function and hence future studies employing more PI-103 sensitive experimental behavioral measures are warranted. Further, while this is the first study to utilize AWSdel to examine gene-brain-behavior relationships, the small sample-size will necessitate replication in future studies. Finally, in contrast to neuroanatomical volumes that are more readily quantified, pinpointing a relationship of these to behavior or cognition is limited by the extent to which a given paradigm mirrors the function of the structure. Therefore, as a first step, we have focused on demonstrating that individuals with AWSdel exhibit structural brain patterns or cognitive profiles that are either consistent or inconsistent with typical WS or TD. Future studies will be useful in refining structure-function relationships in, as well as interactions/connectivity amongst these regions; such studies can help to narrow gene candidates that alter the development or function of specific functional human brain circuits. In summary, we show that the current preliminary study in individuals with rare, atypical deletions associated with WS provide new insights into the neural mechanisms of cognitive function and putative genetic underpinnings.