Identification of rare copy number variants in high burden schizophrenia families

Am J Med Genet B Neuropsychiatr Genet. 2013 Apr;162B(3):273-82. doi: 10.1002/ajmg.b.32146. Epub 2013 Mar 15.


Over the last years, genome-wide studies consistently showed an increased burden of rare copy number variants (CNVs) in schizophrenia patients, supporting the "common disease, rare variant" hypothesis in at least a subset of patients. We hypothesize that in families with a high burden of disease, and thus probably a high genetic load influencing disease susceptibility, rare CNVs might be involved in the etiology of schizophrenia. We performed a genome-wide CNV analysis in the index patients of eight families with multiple schizophrenia affected members, and consecutively performed a detailed family analysis for the most relevant CNVs. One index patient showed a DRD5 containing duplication. A second index patient presented with an NRXN1 containing deletion and two adjacent duplications containing MYT1L and SNTG2. Detailed analysis in the subsequent families showed segregation of the identified CNVs. With this study we show the importance of screening high burden families for rare CNVs, which will not only broaden our knowledge concerning the molecular genetic mechanisms involved in schizophrenia but also allow the use of the obtained genetic data to provide better clinical care to these families in general and to non-symptomatic causal CNV carriers in particular.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Calcium-Binding Proteins
  • Cell Adhesion Molecules, Neuronal / genetics
  • DNA Copy Number Variations*
  • Family Health
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genome-Wide Association Study
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Muscle Proteins / genetics
  • Nerve Tissue Proteins / genetics
  • Neural Cell Adhesion Molecules
  • Pedigree
  • Protein Biosynthesis
  • Receptors, Dopamine D5 / genetics
  • Schizophrenia / genetics*
  • Transcription Factors / genetics


  • Calcium-Binding Proteins
  • Cell Adhesion Molecules, Neuronal
  • DRD5 protein, human
  • MYT1L protein, human
  • Membrane Proteins
  • Muscle Proteins
  • NRXN1 protein, human
  • Nerve Tissue Proteins
  • Neural Cell Adhesion Molecules
  • SNTG2 protein, human
  • Transcription Factors
  • Receptors, Dopamine D5