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| 1 | | Psychiatr. Genet. 2012 Aug 22: 206-9 |
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| PMID | 22547139 |
| Title | Microduplications disrupting the MYT1L gene (2p25.3) are associated with schizophrenia. |
| Abstract | Childhood-onset schizophrenia (COS) is a rare severe form of schizophrenia that may have greater salient genetic risk. Despite evidence for high heritability, conclusive genetic causes of schizophrenia remain elusive. Recent genomic technologies in concert with large case-control cohorts have led to several associations of highly penetrant rare copy number variants (CNVs) and schizophrenia. We previously reported two patients with COS who carried a microduplication disrupting the PXDN and MYT1L genes at 2p25.3. This rate of duplications within our COS population (N=92) is significantly higher than that in 2026 healthy controls (P=0.002). As a replication, we report a meta-analysis of four recently published studies that together provide strong evidence for an association between variably sized microduplications involving the MYT1L gene and schizophrenia. None have reported this separately. Altogether, among 5325 patients and 9279 controls, 10 microduplications were observed: nine in patients and one in a control (odds ratio=15.7, P=0.001). Further, the 2% rate observed in our COS patients is also significantly higher than the rate in adult-onset cases (0.14%, odds ratio=16.6, P=0.01). This report adds to the growing body of literature implicating rare CNVs as risk factors for schizophrenia and shows that some risk CNVs are more common among extreme early-onset cases. |
| SCZ Keywords | schizophrenia |
| 2 | | Psychiatr. Genet. 2012 Jun 22: 137-40 |
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| PMID | 22157634 |
| Title | Germline mosaic transmission of a novel duplication of PXDN and MYT1L to two male half-siblings with autism. |
| Abstract | Autism is a neurodevelopmental disorder with a strong genetic component to susceptibility. In this study, we report the molecular characterization of an apparent de-novo 281 kb duplication of chromosome 2p25.3 in two male half-siblings with autism. The 2p25.3 duplication was first identified through a low-density microarray, validated with fluorescent in-situ hybridization, and duplication breakpoints were delineated using an Affymetrix 6.0 single-nucleotide polymorphism microarray. The fluorescent in-situ hybridization results validated the novel copy number variant and revealed the mother to be mosaic, with ?33% of her lymphoblast cells carrying the duplication. Therefore, the duplication was transmitted through the mechanism of germline mosaicism. In addition, duplication breakpoints were refined and showed that PXDN is fully duplicated, whereas seven exons of the terminal portion of the 25 exon gene MYT1L are within the duplicated region. MYT1L, a gene predominately expressed in the brain, has recently been linked with other neuropsychiatric illness such as schizophrenia and depression. Results from this study indicate that the 2p25.3 duplication disrupting PXDN and MYT1L is a potential autism-causing variant in the pedigree reported here and should receive further consideration as a candidate for autism. |
| SCZ Keywords | schizophrenia |
