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An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities

Kaminsky, Erin B., Kaul, Vineith, Paschall, Justin, Church, Deanna M., Bunke, Brian, Kunig, Dawn, Moreno-De-Luca, Daniel, Moreno-De-Luca, Andres, Mulle, Jennifer G., Warren, Stephen T., Richard, Gabriele, Compton, John G., Fuller, Amy E., Gliem, Troy J., Huang, Shuwen, Collinson, Morag N., Beal, Sarah J., Ackley, Todd, Pickering, Diane L., Golden, Denae M., Aston, Emily, Whitby, Heidi, Shetty, Shashirekha, Rossi, Michael R., Rudd, M Katharine, South, Sarah T., Brothman, Arthur R., Sanger, Warren G., Iyer, Ramaswamy K., Crolla, John A., Thorland, Erik C., Aradhya, Swaroop, Ledbetter, David H. and Martin, Christa L. (2011) An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities Genetics in Medicine, 13, (9), pp. 777-784. (doi:10.1097/GIM.0b013e31822c79f9). (PMID:21844811).

Record type: Article


Purpose: Copy number variants have emerged as a major cause of human disease such as autism and intellectual disabilities. Because copy number variants are common in normal individuals, determining the functional and clinical significance of rare copy number variants in patients remains challenging. The adoption of whole-genome chromosomal microarray analysis as a first-tier diagnostic test for individuals with unexplained developmental disabilities provides a unique opportunity to obtain large copy number variant datasets generated through routine patient care.

Methods: A consortium of diagnostic laboratories was established (the International Standards for Cytogenomic Arrays consortium) to share copy number variant and phenotypic data in a central, public database. We present the largest copy number variant case-control study to date comprising 15,749 International Standards for Cytogenomic Arrays cases and 10,118 published controls, focusing our initial analysis on recurrent deletions and duplications involving 14 copy number variant regions.

Results: Compared with controls, 14 deletions and seven duplications were significantly overrepresented in cases, providing a clinical diagnosis as pathogenic.

Conclusion: Given the rapid expansion of clinical chromosomal microarray analysis testing, very large datasets will be available to determine the functional significance of increasingly rare copy number variants. This data will provide an evidence-based guide to clinicians across many disciplines involved in the diagnosis, management, and care of these patients and their families.

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Published date: September 2011
Organisations: Human Development & Health


Local EPrints ID: 196367
ISSN: 1098-3600
PURE UUID: 99949227-1df8-4048-9fb9-59c760943110

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Date deposited: 06 Sep 2011 14:19
Last modified: 18 Jul 2017 11:23

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Author: Erin B. Kaminsky
Author: Vineith Kaul
Author: Justin Paschall
Author: Deanna M. Church
Author: Brian Bunke
Author: Dawn Kunig
Author: Daniel Moreno-De-Luca
Author: Andres Moreno-De-Luca
Author: Jennifer G. Mulle
Author: Stephen T. Warren
Author: Gabriele Richard
Author: John G. Compton
Author: Amy E. Fuller
Author: Troy J. Gliem
Author: Shuwen Huang
Author: Morag N. Collinson
Author: Sarah J. Beal
Author: Todd Ackley
Author: Diane L. Pickering
Author: Denae M. Golden
Author: Emily Aston
Author: Heidi Whitby
Author: Shashirekha Shetty
Author: Michael R. Rossi
Author: M Katharine Rudd
Author: Sarah T. South
Author: Arthur R. Brothman
Author: Warren G. Sanger
Author: Ramaswamy K. Iyer
Author: John A. Crolla
Author: Erik C. Thorland
Author: Swaroop Aradhya
Author: David H. Ledbetter
Author: Christa L. Martin

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