Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia
Open accessAbstract
Copy number variations (CNVs) account for a substantial proportion of human genomic variation, and have been shown to cause neurodevelopmental disorders. We sought to determine the relevance of CNVs to the aetiology of schizophrenia (SZ). Whole-genome, high-resolution, tiling path BAC array comparative genomic hybridization (array CGH) was employed to test DNA from 93 individuals with DSM-IV SZ. Common DNA copy number changes that are unlikely to be directly pathogenic in SZ were filtered out by comparison to a reference dataset of 372 control individuals analyzed in our laboratory, and a screen against the Database of Genomic Variants. The remaining aberrations were validated with Affymetrix 250K SNP arrays or 244K Agilent oligo-arrays and tested for inheritance from the parents. A total of 13 aberrations satisfied our criteria. Two of them are very likely to be pathogenic. The first one is a deletion at 2p16.3 that was present in an affected sibling and disrupts NRXN1. The second one is a de novo duplication at 15q13.1 spanning APBA2. The proteins of these two genes interact directly and play a role in synaptic development and function. Both genes have been affected by CNVs in patients with autism and mental retardation, but neither has been previously implicated in SZ.
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Deletions of NRXN1 point to the importance of as yet unspecified abnormalities of synaptic function in the disorder.
“Important exceptions are deletions of NRXN1, encoding the presynaptic neuronal cell adhesion molecule neurexin 1,11, 15 pointing to the importance of as yet unspecified abnormalities of synaptic function in the disorder.”
From De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia (2012) · cites this paper as [15]
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Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1
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- Authors
- Kirov, G., Gumus, D., Chen, W., Norton, N., Georgieva, L., Sari, M., O'Donovan, M. C., Erdogan, F., Owen, M. J., Ropers, H.-H., & Ullmann, R.
- Affiliations
- Cardiff University (GB)
- Max Planck Society (DE)
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-10-03
- Volume
- 17
- Issue
- 3
- Pages
- 458-465
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2108284636
- Cited by
- 377
- References
- 56
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 8 · 2020: 11 · 2019: 13 · 2018: 7 · 2017: 11 · 2016: 14 · 2015: 24 · 2014: 25 · 2013: 30 · 2012: 35
- FWCI
- 23.94
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Max Planck Institute for Plasma Physics (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Wellcome Trust
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- schizophrenia, copy number variation, NRXN1, de novo duplication, synaptic development, neurodevelopmental disorders, genetic interactions
- MeSH terms
- Adolescent, Adult, Autistic Disorder, Carrier Proteins, Chromosomes, Human, Pair 15, Female, Glycoproteins, Humans, Male, Intellectual Disability, Middle Aged, Nerve Tissue Proteins, Neuropeptides, Nucleic Acid Hybridization, Schizophrenia, Genetic Variation, Cadherins, Case-Control Studies, Gene Dosage
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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