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Rare mutations tied to schizophrenia

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11:11am, April 2, 2008
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DNA mutations that likely disrupt brain development occur at relatively high rates in people with schizophrenia, according to data jointly reported by two research teams.

These genetic mutations, many of which are critically situated in genes that have been implicated in various facets of brain development, were present in 15 percent of people diagnosed with schizophrenia in young adulthood or later and in 20 percent of those diagnosed with the severe mental disorder before age 13, the scientists report in an investigation published online March 27 in Science.

There was no one combination of mutations that characterized all the people with schizophrenia. Rather, most people displayed their own unique genetic alterations.

In contrast, novel genetic deletions and duplications appeared in only 5 percent of people who had no psychiatric ailments.

A team led by geneticist Jonathan Sebat of Cold Spring Harbor Laboratory in New York analyzed DNA from 150 adults with schizophrenia and 268 adults who were free of psychiatric illness. Most genetic deletions and duplications linked to schizophrenia were unique to each individual.

Psychiatrist Judith L. Rapoport of the National Institute of Mental Health in Bethesda, Md., and her coworkers examined DNA from 83 youngsters with schizophrenia and from 154 of their parents. Individually rare mutations showed a slightly stronger link to childhood-onset schizophrenia than they did to adult-onset schizophrenia. Most of the alterations associated with the childhood-onset disorder appeared to have been inherited, some from parents who showed no signs of schizophrenia.

These findings come after evidence, reported earlier by Sebat's group, that many children with autism possess individually rare genetic mutations that form spontaneously rather than being inherited (SN: 3/24/07, p. 189).

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