Scientists hope that identifying the underlying mechanisms affected by the missing or duplicated piece of DNA will provide new targets for drug development. But at this point, it’s not clear whether it’s one gene or several that raise the risk of disease, or how deletions and duplications of the same piece of DNA can trigger outcomes as different as schizophrenia and mental retardation.
The findings do hint that autism, schizophrenia, and mental retardation have common biological underpinnings, a conclusion that has some precedent. Children with mental retardation often have psychiatric and behavioral problems as well, although these may be undiagnosed or underappreciated in the face of their cognitive deficits. And some families may have a history of mental illness, but not of a specific illness.
Mental retardation, autism, and (to some extent) schizophrenia are developmental diseases, diagnosed in childhood or adolescence. So identifying a common biological flaw may shed light on the crucial components of neural development and suggest ways to help when that development goes awry. Perhaps a disruption in the 1q21.1 region of the chromosome inherited from one parent can send some fundamental developmental process off course. The ultimate impact might depend on environmental factors, variations in other parts of the genome, or the version of the gene inherited from the other parent. Someone whose genome has mistakes in other regions that are important for brain development and cognitive function might end up with mental retardation. Someone whose genome is largely intact, but who has a mutation in a gene linked to autism, may end up with high-functioning autism.
A better understanding of the molecular consequences of errors in 1q21.1 and other recently identified hot spots may help redefine autism and schizophrenia and even change the way they are diagnosed. Both disorders cause a wide range of symptoms, and they are currently identified through behavioral and cognitive tests. Physicians may now be able to augment that diagnosis with the results of genetic testing. Only a small percentage of people with autism or schizophrenia will carry a particular genetic variation. But researchers hope that as more copy number variations are linked to these disorders, such genetic characterizations will become useful tools for predicting the best treatment for a given patient.
“At one time in the history of medicine, when you had a cough and an infection of the lungs, they called it pneumonia,” says James Lupski, a physician and scientist at Baylor College of Medicine. Now we know that pneumonia is actually a group of different diseases, both bacterial and viral, that must each be treated differently. Eventually, someone developed a way to distinguish bacterial pneumonia from other forms, Lupski says, and that set the stage for the development of different treatments.
A diagnostic test that can detect copy number variations already exists: array CGH, the same test scientists use in research studies. It is currently used in clinical genetics labs to diagnose unexplained cases of mental retardation, developmental delay, and, increasingly, autism as well. It’s not yet clear how to use the results to guide treatment–especially in disorders such as autism, for which no drugs are available to treat the root cause. But when it comes to other disorders, scientists are optimistic. “We have lots of effective psychiatric drugs, but it often takes weeks to find the right one,” says Lupski. “Could this simple characterization predict the one that works best? That alone would be of tremendous benefit to patients.”