| 1 | Proc. Natl. Acad. Sci. U.S.A. 2010 Jun 107: 10584-9 |
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| PMID | 20489179 |
| Title | Strong synaptic transmission impact by copy number variations in schizophrenia. |
| Abstract | schizophrenia是一个精神障碍,发作late adolescence and unclear etiology characterized by both positive and negative symptoms, as well as cognitive deficits. To identify copy number variations (CNVs) that increase the risk ofschizophrenia, we performed a whole-genome CNV analysis on a cohort of 977schizophreniacases and 2,000 healthy adults of European ancestry who were genotyped with 1.7 million probes. Positive findings were evaluated in an independent cohort of 758schizophreniacases and 1,485 controls. The Gene Ontology synaptic transmission family of genes was notably enriched for CNVs in the cases (P = 1.5 x 10(-7)). Among these, CACNA1B andDOC2A, both calcium-signaling genes responsible for neuronal excitation, were deleted in 16 cases and duplicated in 10 cases, respectively. In addition, RET and RIT2, both ras-related genes important for neural crest development, were significantly affected by CNVs. RET deletion was exclusive to seven cases, and RIT2 deletions were overrepresented common variant CNVs in theschizophreniacases. Our results suggest that novel variations involving the processes of synaptic transmission contribute to the genetic susceptibility ofschizophrenia. |
| SCZ Keywords | schizophrenia |
| 2 | Am. J. Med. Genet. A 2010 Jun 152A: 1567-74 |
| PMID | 20503337 |
| Title | Duplication 16p11.2 in a child with infantile seizure disorder. |
| Abstract | Submicroscopic recurrent 16p11.2 rearrangements are associated with several neurodevelopmental disorders, including autism, mental retardation, andschizophrenia. The common 16p11.2 region includes 24 known genes, of which 22 are expressed in the developing human fetal nervous system. As yet, the mechanisms leading to neurodevelopmental abnormalities and the broader phenotypes associated with deletion or duplication of 16p11.2 have not been clarified. Here we report a child with spastic quadriparesis, refractory infantile seizures, severe global developmental delay, hypotonia, and microcephaly, and a de novo 598 kb 16p11.2 microduplication. Family history is negative for any of these features in parents and immediate family members. Sequencing analyses showed no mutations inDOC2A, QPRT, and SEZ6L2, genes within the duplicated 16p11.2 region that have been implicated in neuronal function and/or seizure related phenotypes. The child's clinical course is consistent with a rare seizure disorder called malignant migrating partial seizure disorder of infancy, raising the possibility that duplication or disruption of genes in the 16p11.2 interval may contribute to this severe disorder. |
| SCZ Keywords | schizophrenia |