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Pescosolido MF, Gamsiz ED, Nagpal S, et al. Distribution of disease-associated copy number variants across distinct disorders of cognitive development. J Am Acad Child Adolesc Psychiatry. 2013;52(4):414-430.e14doi: 10.1016/j.jaac.2013.01.003.
Pescosolido, M. F., Gamsiz, E. D., Nagpal, S., & Morrow, E. M. (2013). Distribution of disease-associated copy number variants across distinct disorders of cognitive development. Journal of the American Academy of Child and Adolescent Psychiatry, 52(4), 414-430.e14. https://doi.org/10.1016/j.jaac.2013.01.003
Pescosolido, Matthew F, et al. "Distribution of disease-associated copy number variants across distinct disorders of cognitive development." Journal of the American Academy of Child and Adolescent Psychiatry vol. 52,4 (2013): 414-430.e14. doi: https://doi.org/10.1016/j.jaac.2013.01.003
Pescosolido MF, Gamsiz ED, Nagpal S, Morrow EM. Distribution of disease-associated copy number variants across distinct disorders of cognitive development. J Am Acad Child Adolesc Psychiatry. 2013 Apr;52(4):414-430.e14. doi: 10.1016/j.jaac.2013.01.003. PMID: 23582872; PMCID: PMC3774163.
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J Am Acad Child Adolesc Psychiatry. 2013 Apr;52(4):414-430.e14. doi: 10.1016/j.jaac.2013.01.003.

Distribution of disease-associated copy number variants across distinct disorders of cognitive development.

Journal of the American Academy of Child and Adolescent Psychiatry

Matthew F Pescosolido, Ece D Gamsiz, Shailender Nagpal, Eric M Morrow

Affiliations

  1. Institute for Brain Science at Brown University, Providence, RI 02912, USA.

PMID: 23582872 PMCID: PMC3774163 DOI: 10.1016/j.jaac.2013.01.003

Abstract

OBJECTIVE: The purpose of the present study was to discover the extent to which distinct DSM disorders share large, highly recurrent copy number variants (CNVs) as susceptibility factors. We also sought to identify gene mechanisms common to groups of diagnoses and/or specific to a given diagnosis based on associations with CNVs.

METHOD: Systematic review of 820 PubMed articles on autism spectrum disorder (ASD), intellectual disability (ID), schizophrenia, and epilepsy produced 54 CNVs associated with one or several disorders. Pathway analysis on genes implicated by CNVs in different groupings was conducted.

RESULTS: The majority of CNVs were found in ID with the other disorders somewhat subsumed, yet certain CNVs were associated with isolated or groups of disorders. Based on genes implicated by CNVs, ID encompassed 96.8% of genes in ASD, 92.8% of genes in schizophrenia, and 100.0% of genes in epilepsy. Pathway analysis revealed that synapse processes were enriched in ASD, ID, and schizophrenia. Disease-specific processes were identified in ID (actin cytoskeleton processes), schizophrenia (ubiquitin-related processes), and ASD (synaptic vesicle transport and exocytosis).

CONCLUSIONS: Intellectual disability may arise from the broadest range of genetic pathways, and specific subsets of these pathways appear to be relevant to other disorders or combinations of these disorders. It is clear that statistically significant CNVs across disorders of cognitive development are highly enriched for biological processes related to the synapse. There are also disorder-specific processes that may aid in understanding the distinct presentations and pathophysiology of these disorders.

Copyright © 2013 American Academy of Child & Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

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