Velocardiofacial syndrome is a genetic disorder associated with a microdeletion on the long arm of chromosome 22, and this segment is responsible for coding catechol-O-methyltransferase, an enzyme involved in dopamine degradation.
Several lines of evidence have implicated the catechol-O-methyltransferase (COMT) gene as a candidate for schizophrenia (SZ) susceptibility, not only because it encodes a key dopamine catabolic enzyme but also because it maps to the velocardiofacial syndrome region of chromosome 22q11 which has long been associated with SZ predisposition.
The gene encoding catechol-O-methyltransferase (COMT) is a strong candidate for schizophrenia susceptibility, owing to the role of COMT in dopamine metabolism, and the location of the gene within the deleted region in velocardiofacial syndrome, a disorder associated with high rates of schizophrenia.
One of these is its biochemical function in metabolism of catecholamine neurotransmitters; another is the microdeletion, on chromosome 22q11, that includes the COMT gene and causes velocardiofacial syndrome, a syndrome associated with a high rate of psychosis, particularly schizophrenia.
The gene for COMT is located on chromosome 22q11, an area that has been implicated in the pathogenesis of schizophrenia through linkage studies and through the detection of deletions in schizophrenics and velocardiofacial syndrome patients that often present psychotic symptomatology.
These data suggest that the COMT gene does not play a major role in the pathogenesis of schizophrenia, and the genotypic overlap between schizophrenia and velocardiofacial syndrome was rare in this cohort.