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Neurexin 1 (NRXN1) is a presynaptic neuronal adhesion molecule that interacts with postsynaptic neuroligins in both glutamatergic and GABAergic synapses and is important in synaptic formation and function. NRXN1 deletions increase the risk of schizophrenia, so our aims were to explore this in our family sample, to distinguish de novo from inherited mutations, to examine transmission to affected and unaffected siblings and to estimate penetrance. We performed copy number analyses in NRXN1 using data from Illumina BeadArrays from 635 subjects with schizophrenia (276 in genotyped families), 487 of their unaffected parents and 309 unaffected siblings as well as 635 normal controls, all from the CBDB/NIMH Genetic Study of Schizophrenia. Deletions called by software were confirmed by quantitative PCR and comparative genome hybridization. There were deletions in 15 individuals in 11 families, including de novo exonic deletions in one case and one unaffected sibling. We observed no deletions in controls, 7 deletions in cases (1.10%), and an unexpectedly high deletion frequency in parents (n=5, 1.02%) and siblings (n=3, 0.97%). Three families showed inheritance from an unaffected parent, and in two families an unaffected parent did not transmit to the affected offspring. Thus we have added to the evidence that NRXN1 deletions are more frequent in patients with schizophrenia than in healthy individuals. However, the presence of de novo deletions in unaffected relatives and transmission from and to unaffected family members demonstrated that while the deletions may well have been necessary for some carriers to develop schizophrenia, they were not always sufficient., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Prior studies have found decreased mRNA expression of oligodendrocyte-associated genes in the dorsolateral prefrontal cortex (DLPFC) of patients with schizophrenia. However, it is unclear which specific genes are affected and whether the changes occur in the cortical white or grey matter. We assessed the mRNA expression levels of four oligodendrocyte-related genes: myelin-associated basic protein (MOBP), myelin-associated glycoprotein (MAG), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) and oligodendrocyte-lineage transcription factor 2 (OLIG2) in DLPFC white and grey matter using quantitative-PCR (approximately 70 controls and approximately 30 patients with schizophrenia). We also examined the effects of high-risk polymorphisms in CNP and OLIG2 on mRNA levels of these genes. We found that genetic polymorphisms in CNP (rs2070106) and OLIG2 (rs1059004 and rs9653711), previously associated with schizophrenia, predicted low expression of these genes. Expression of MAG, CNP and OLIG2 did not differ between patients with schizophrenia and controls in the grey or white matter but MOBP mRNA levels were increased in the DLPFC white matter in patients with a history of substance abuse. MOBP and CNP protein in the white matter was not altered. Although previously reported reductions in the expression of myelin-related genes in the DLPFC were not detected, we show that individuals carrying risk-associated alleles in oligodendrocyte-related genes had relatively lower transcript levels. These data illustrate the importance of genetic background in gene expression studies in schizophrenia.