De Novo Gene Mutations Occur In Half of Sporadic Cases of Schizophrenia

by Dr Sam Girgis on August 9, 2011

Schizophrenia is a psychiatric disorder that is characterized by disorganized thought processes and emotional lability.  The most common symptoms of this mental illness are auditory and visual hallucinations, paranoia, and delusions.  It is often associated with significant dysfunction in both interpersonal relationships and on an occupational level.  The condition occurs worldwide at a rate of 0.7 to 1.0 % of the population.  There are many factors that are thought to contribute to the development of the disorder and they include genetic, environmental, psychological, and social factors.  There is a strong genetic component and the disorder has a familial predisposition.  There are also a large number of cases that occur on a sporadic basis and are present in families that do not have any psychiatric illness among their members.  Researchers lead by Dr. Maria Karayiorgou have discovered that de novo gene mutations occur in approximately half of the sporadic cases of schizophrenia.  The results of their research were published online in the journal Nature Genetics.  The researchers performed DNA sequencing of the exomes, or protein coding regions, from 53 individuals with sporadic schizophrenia or schizoaffective disorder.  In addition, the researchers performed DNA exome sequencing in 22 unaffected control individuals.  Parents from both controls and patients were sequenced as well.  There were 40 de novo mutations in 27 schizophrenia cases affecting 40 different genes.  One of the mutations occurred in the DGCR2 gene which is located in a region of chromosome 22 which is thought to be associated with schizophrenia.  A large number of the mutations were shown to affect the protein structure and function of the mutated gene products.  The authors wrote, “Our analyses suggest a major role for de novo mutations in schizophrenia as well as a large mutational target, which together provide a plausible explanation for the high global incidence and persistence of the disease… We propose that this large number of targets that, when mutated, can give rise to schizophre­nia, along with the relatively high rate of protein-altering mutations empirically shown in this study, provides a plausible explanation for both the high global incidence and the persistence of schizophrenia despite extremely variable environmental factors, severely reduced fecundity and increased mortality. Our findings are an important step toward understanding the pathogenesis of the disease and emphasize the challenge in determining the neural substrates that these diverse genetic risk factors converge upon to generate a common pattern of clinical dysfunction and symptoms”.  Future studies will focus on the exact contribution of each of the identified gene mutations in the pathogenesis of the disorder.  These research findings may help identify alternative  medication targets for the treatment of this debilitating disorder.


Bin Xu et al. “Exome sequencing supports a de novo mutational paradigm for schizophreniaNature Genetics published online August 7, 2011 doi:10.1038/ng.902

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