Prevalence of 22q11.2 deletions in 311 Dutch patients with schizophrenia

Abstract

The objectives of this study were 1) to examine whether the prevalence of 22q11.2 deletion syndrome (22q11DS) in schizophrenia patients with the Deficit syndrome is higher than the reported ~2% for the population of schizophrenia patients as a whole, and 2) to estimate the overall prevalence of 22q11DS among schizophrenia patients by combining all available studies. Our sample, enriched for patients with the Deficit syndrome, had 88% power to detect an estimated prevalence of 5% of 22q11.2 deletions. No 22q11.2 deletions were detected in 311 schizophrenia patients, 146 of whom met criteria for the Deficit syndrome. Our literature research revealed that in eight studies sixteen deletions were identified in 2133 patients with schizophrenia. This corresponds to a prevalence of 0.75% (95%CI: 0.5%-1.2%). In conclusion: The prevalence of 22q11.2DS in schizophrenia patients with the Deficit syndrome is not higher than in the population of schizophrenia patients as a whole. The prevalence of 22q11.2DS in schizophrenia patients is lower than the frequently reported prevalence of 2% or more.

High rate of disease-related copy number variations in childhood onset schizophrenia

“…Most strikingly, five patients (4.0%) carried a microdeletion in the chromosome 22q11.2 region, a recognized risk factor for schizophrenia, autism and other neurodevelopmental disorders. 33–35 The frequency of this microdeletion in COS probands (4.0%) was significantly higher than the frequency in healthy controls (0.2% vs 4.0%, P <0.0001) 36 and was also higher than the previously reported frequency in AOS patients (0.3–1%) 37–39 ( P <0.0001). Because 20% of our COS patients had prepsychotic autism spectrum disorder, 40 we were particularly interested in the prepsychotic developmental pattern of our COS probands with the 22q11.2 deletion.…”

Genome Arrays for the Detection of Copy Number Variations in Idiopathic Mental Retardation, Idiopathic Generalized Epilepsy and Neuropsychiatric Disorders: Lessons for Diagnostic Workflow and Research

“…The 22q11.2 deletion syndrome is an example of a well-established, recurrent chromosomal abnormality that is associated with a variable phenotypic expression that commonly includes schizophrenia [Bassett et al, 2008]. It has been estimated that about 0.75% of patients with schizophrenia have the 22q11.2 deletion [Hoogendoorn et al, 2008]. The deletion region contains several genes that are considered to be candidate genes for schizophrenia, such as PRODH , GNB1L , COMT , and PI4KA [Prasad et al, 2008;Vorstman et al, 2009].…”

Redox Dysregulation and Oxidative Stress in Schizophrenia: Nutrigenetics as a Challenge in Psychiatric Disease Prevention

“…Results from several genome-wide scans [5][6][7][8] have identified chromosomal regions of interest, and cumulative evidence from replication efforts suggest that schizophrenia susceptibility genes may be found on chromosomes 1, 6, 8, 10, 13 and 22 [see reviews in [9][10][11]. Very recent studies from large genome-wide scans in multiple, large cohorts that have identified both rare high-risk mutations (RR: 2-14) [12][13][14][15] and common low-risk variations on chromosome 2 (ZnF804A) and 11 (RR: 1.09-1.19) [16] and in the HLA and histone regions on chromosome 6 [17]. Similarly, studies that have adopted a family-based approach have identified a balanced translocation that disrupts the DISC1 gene [18], as well as the neuregulin gene [19], while hypothesis-driven approaches based on biological findings of deficits in the ability to cope with oxidative stress in patients with schizophrenia have implicated gene variants in the biosynthesis of glutathione as susceptibility factors of the illness [20,21].…”