Renal Cysts and Diabetes Syndrome, Autism, and Schizophrenia Linked

Researchers whose study results were published yesterday in the American Journal of Human Genetics have uncovered a small genomic deletion in patients with autism spectrum disorders (ASD) and schizophrenia. The region in which the deletion occurs also includes a gene (HNF1B)that when mutated is know to cause renal cysts and diabetes syndrome (RCAD).

"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," said lead author Dr. Daniel Moreno-De-Luca.

Working with a team of investigators, Moreno-De-Luca analyzed the DNA of 23,000 patients with ASD, developmental delay, or schizophrenia to find DNA duplications or deletions (copy-number variants). In 24 patients, the researchers found the same deletion on chromosome 17 (17q12 to be exact), a CNV that was absent in 52,448 controls.

"We calculate the risk for this combined sample (ASD and schizophrenia) to be at least 13.58, and probably much higher," said Dr. David H. Ledbetter, Emory University.

The gene highlighted in the current study is one of 15 contained within the deletion. What’s interesting is that many patients with ASD in the study had a family history of kidney

disease and/or diabetes. Additionally, patients with RCAD often present with neurodevelopmental disorders.

"The phenotypic spectrum of patients with the 17q12 deletion is consistent with a gene syndrome that extends beyond RCAD," said Dr. Moreno-De-Luca. "We have uncovered a recurrent pathogenic CNV that confers a very high risk for ASD, schizophrenia, and neorodevelopmental disorders."

The authors concluded that at least one of the 15 genes in the deleted interval is essential for normal neurocognitive development and function.

Can genetic testing help diagnose patients with a family history of renal disease who might be at risk of developing schizophrenia or autism? Should patients with RCAD be automatically screened for ASD and schizophrenia, and vice versa?