The contribution of 7q33 copy number variations for intellectual disability


Copy number variations (CNVs) at the 7q33 cytoband are very rarely described in the literature, and almost all of the cases comprise large deletions affecting more than just the q33 segment. We report seven patients (two families with two siblings and their affected mother and one unrelated patient) with neurodevelopmental delay associated with CNVs in 7q33 alone. All the patients presented mild to moderate intellectual disability (ID), dysmorphic features, and a behavioral phenotype characterized by aggressiveness and disinhibition. One family presents a small duplication in cis affecting CALD1 and AGBL3 genes, while the other four patients carry two larger deletions encompassing EXOC4, CALD1, AGBL3, and CNOT4. This work helps to refine the phenotype and narrow the minimal critical region involved in 7q33 CNVs. Comparison with similar cases and functional studies should help us clarify the relevance of the deleted genes for ID and behavioral alterations.

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We would like to thank all the patients and their families for their participation in the genetic studies and for allowing this publication. We would also like to acknowledge the DECIPHER Consortium, Database of Genomic Variants, and OMIM since this study makes use of data generated by these platforms.


This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the projects PIC/IC/83026/2007, PIC/IC/83013/2007, and POCI-01-0145-FEDER-007038. This work has also been funded by the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). FL was supported by Foundation for Science and Technology (FCT) through the fellowship SFRH/BD/90167/2012.

Author information




FL, FT, SS, and PR performed the molecular studies and analyzed the molecular data. AMF, SAL, AJ, and JS collected clinical data. FL, FT, and PM drafted the paper. PM obtained funding for this study. The study was performed under the direction of PM.

Corresponding author

Correspondence to Patrícia Maciel.

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The authors declare that they have no conflict of interest.

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Lopes, F., Torres, F., Lynch, S.A. et al. The contribution of 7q33 copy number variations for intellectual disability. Neurogenetics 19, 27–40 (2018).

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  • 7q33 CNVs
  • CALD1
  • AGBL3
  • EXOC4
  • CNOT4
  • Duplication