At least ten percent of non-familial cases of schizophrenia may be due to spontaneous mutation resulting in loss or gain of multiple genes within chromosomes, according to an article published online May 30 by Nature Genetics.

Researchers scanned the genome of 1,077 people for copy number mutations: 152 people with schizophrenia, 159 people without schizophrenia, and both biological parents.

A total of 15 people with schizophrenia had mutations involving either a gain or loss of genes that were not present in the chromosomes of either biological unaffected parent. Only two such mutations were found in people without schizophrenia. Study subjects were from the European-origin Afrikaner population in South Africa, a genetically homogenous population that is ideal for genetic evaluation.

"We now know the cause of around 10 percent of the cases of sporadic schizophrenia," said Maria Karayiorgou, MD, professor of psychiatry, Columbia University Medical Center, the senior author on the study. "Schizophrenia is not as much of a 'big black box' as it used to be. The identification of these genes lets us know what brain development pathways are involved in disease onset, so that in the future we can look at better ways of treating this devastating disease."

One of the new or de novo mutations researchers found in more than one affected individual in this study was a deletion of a region of chromosome 22. Karayiorgou had previously provided evidence that loss of genes in this region, 22q11.2, was responsible for causing sporadic cases of schizophrenia in the population. The current finding confirms 22q11.2 as the only known recurrent such mutation linked to schizophrenia.

"Such abnormal deletions or duplications of genetic material are increasingly being implicated in schizophrenia and autism," explains National Institute of Mental Health Director Thomas R. Insel, MD. "Now we have a dramatic demonstration that genetic vulnerabilities for these illnesses may stem from both hereditary and non-hereditary processes. This line of research holds promise for improved treatments - and perhaps someday even prevention - of developmental brain disorders."

Karayiorgou and co-senior author Joseph A. Gogos, M.D., Ph.D., associate professor of physiology and neuroscience at Columbia University Medical Center, agree that the goal is for psychiatrists to be able to inform patients that they have a mutation that is causing their disease and ultimately to be able to tailor treatments to individual patients based on their specific mutation. This tailored treatment is in the future, according to Karayiorgou, but she says patients and their families are relieved to know that there is a biological cause of their illness.

The researchers plan to extend their screen for additional de novo mutations by using increased resolution scans to study additional families. They also plan to scrutinize further genes affected by the identified mutations through human genetics and animal model approaches.