New Copy Number Variations in Schizophrenia

Genome-wide screenings for copy number variations (CNVs) in patients with schizophrenia have demonstrated the
presence of several CNVs that increase the risk of developing the disease and a growing number of large rare CNVs; the
contribution of these rare CNVs to schizophrenia remains unknown. Using Affymetrix 6.0 arrays, we undertook a systematic
search for CNVs in 172 patients with schizophrenia and 160 healthy controls, all of Italian origin, with the aim of confirming
previously identified loci and identifying novel schizophrenia susceptibility genes. We found five patients with a CNV
occurring in one of the regions most convincingly implicated as risk factors for schizophrenia: NRXN1 and the 16p13.1
regions were found to be deleted in single patients and 15q11.2 in 2 patients, whereas the 15q13.3 region was duplicated in
one patient. Furthermore, we found three distinct patients with CNVs in 2q12.2, 3q29 and 17p12 loci, respectively. These
loci were previously reported to be deleted or duplicated in patients with schizophrenia but were never formally associated
with the disease. We found 5 large CNVs (.900 kb) in 4q32, 5q14.3, 8q23.3, 11q25 and 17q12 in five different patients that
could include some new candidate schizophrenia susceptibility genes. In conclusion, the identification of previously
reported CNVs and of new, rare, large CNVs further supports a model of schizophrenia that includes the effect of multiple,
rare, highly penetrant variants.