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Lancet. 2002 Feb 2;359(9304):426-30.

Schizophrenia and velo-cardio-facial syndrome.

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  • 1Division of Psychological Medicine, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK.


Velo-cardio-facial syndrome (VCFS), the most frequent known interstitial deletion identified in man, is associated with chromosomal microdeletions in the q11 band of chromosome 22. The VCFS phenotype is complex, with multiple congenital abnormalities affecting several tissues and organs, many of which are derived from neural crest cells. Although phenotypic variability occurs, individuals with VCFS have high rates of psychiatric disorder, especially schizophrenia. Additionally, an increased prevalence of chromosome 22q11 deletions has been reported in populations of people with schizophrenia. Furthermore, results of molecular genetic studies suggest that a schizophrenia susceptibility locus maps to chromosome 22q. These data indicate that aside from being the child of two parents with schizophrenia or the monozygotic co-twin of an affected individual, VCFS and deletion 22q11 represents the highest known risk factor for the development of schizophrenia. Since the entire sequence of chromosome 22 has now been identified, the study of VCFS offers a timely and uniquely powerful opportunity to identify susceptibility genes for schizophrenia in the general population. Furthermore, the strength of the association between schizophrenia and VCFS has important implications for the clinical management of these disorders.

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