ASDs include a range of neurodevelopmental conditions that are being diagnosed at an increasing rate. The Center for Disease Control and Prevention estimates that ASD currently affects 1 in 110 people. The prevalence of schizophrenia, with a diagnostic rate of 1 in 100 to 1 in 20, is similar. ASD and schizophrenia affect males more often than females, and both are thought to have a strong and overlapping genetic component. "The genetic overlap between ASD and schizophrenia, both of which have a high heritability, has been the focus of several recent studies; however, no single specific genetic cause accounts for more than 1%-2% of cases" says Dr. Daniel Moreno-De-Luca, the lead author of the study.
Dr. Moreno-De-Luca and colleagues analyzed genomic DNA from more than 23,000 patients with ASD, developmental delay, or schizophrenia. They were looking for DNA duplications or deletions referred to as copy-number variants (CNV). Remarkably, they found the same deletion on chromosome 17 in 24 separate patients. This CNV was absent in 52,448 controls, making the finding statistically significant. "We calculate the risk for this combined sample (ASD and schizophrenia) to be at least 13.58, and probably much higher," says Dr. David H. Ledbetter of Emory University. An odds ratio of 13.58 means that someone with this deletion is 13.58 times more likely to develop ASD or schizophrenia than is someone lacking this CNV.
The gene highlighted in this study is one of 15 contained within the deletion. Mutations in HNF1B have been associated with RCAD, and a number of the studied ASD patients were found to have a family history of kidney disease and/or diabetes. Conversely, RCAD patients often present with neurodevelopmental disorders. "The phenotypic spectrum of patients with the 17q12 deletion is consistent with a gene syndrome that extends beyond RCAD," says Dr. Moreno-De-Luca. "We have uncovered a recurrent pathogenic CNV that confers a very high risk for ASD, schizophrenia, and neorodevelopmental disorders." These data suggest that one or more of the 15 genes are critical for neorocognitive development.