New Copy Number Variations in Schizophrenia

Abstract

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.

Genome-Wide Survey of Large Rare Copy Number Variants in Alzheimer’s Disease Among Caribbean Hispanics

“…For example, in case NY1811 (age at onset 73), we observed a 1.9 Mb duplication on chr 2p16.3 ( Figure S2A) encompassing the entire neurexin1 gene (NRXN1) that encodes a neuronal cell surface protein involved in cell recognition and cell adhesion. Genome-wide CNV studies previously implicated NRXN1 deletions in autism and schizophrenia (Ching et al 2010;Magri et al 2010). Our study is the first report describing a duplication of NRXN1 in an AD case.…”

An environmental analysis of genes associated with schizophrenia: hypoxia and vascular factors as interacting elements in the neurodevelopmental model

“…[86][87][88][89] A flood of new genomic data has emerged from these studies. 77,79,[90][91][92][93][94][95][96][97] An increased number and/or size of CNVs has been reported for schizophrenia. [86][87][88][89] Genes identified in CNV studies are of interest for our analysis.…”

Genetic variability in scaffolding proteins and risk for schizophrenia and autism-spectrum disorders: a systematic review

“…Moreover, deletion of the chromosomic region 8p23.3 has been detected in patients with schizophrenia and patients with autism-spectrum disorders. This deletion and other CNVs spanning this gene have been found in patients with Sanders et al 45 Purcell et al 50 Kirov et al 57 Pinto et al 147 Levinson et al 148 Mulle et al 149 Magri et al 150 Szatkiewicz et al 151 Quintero-Rivera et al 152 Levy et al 153 Willatt et al 154 Ballif et al 155 Sagar et al 57 Cuscó et al 157 Walsh et al 158 Egger et al Duplication of 1436299_1642837 has been associated with intellectual disability 40 Deletion of 8p23.3 has been associated with intellectual disability 161 Guilmatre et al 40 Pinto et al 60 Pinto et al 147 Chien et al 161 Szatmari et al 162 Costain et al 163 Marshall et al 164 Ozgen et al 165 …”

“…Variants in different scaffolding genes, either at the allelic or the gene level, may dysregulate the homeostasis of the PSD, which is finally expressed as features associated with different neurodevelopment disorders. In addition Sanders et al 45 Purcell et al 50 Kirov et al 57 Levinson et al 148 Mulle et al 149 Magri et al 150 Szatkiewicz et al 151 Quintero-Rivera et al 152 Levy et al 153 Willatt et al 154 Ballif et al 155 Sagar et al…”