Document Detail


An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities.
MedLine Citation:
PMID:  21844811     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Erin B Kaminsky; Vineith Kaul; Justin Paschall; Deanna M Church; Brian Bunke; Dawn Kunig; Daniel Moreno-De-Luca; Andres Moreno-De-Luca; Jennifer G Mulle; Stephen T Warren; Gabriele Richard; John G Compton; Amy E Fuller; Troy J Gliem; Shuwen Huang; Morag N Collinson; Sarah J Beal; Todd Ackley; Diane L Pickering; Denae M Golden; Emily Aston; Heidi Whitby; Shashirekha Shetty; Michael R Rossi; M Katharine Rudd; Sarah T South; Arthur R Brothman; Warren G Sanger; Ramaswamy K Iyer; John A Crolla; Erik C Thorland; Swaroop Aradhya; David H Ledbetter; Christa L Martin
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural    
Journal Detail:
Title:  Genetics in medicine : official journal of the American College of Medical Genetics     Volume:  13     ISSN:  1530-0366     ISO Abbreviation:  Genet. Med.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-02     Completed Date:  2012-03-27     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  9815831     Medline TA:  Genet Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  777-84     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Cytogenetic Analysis
DNA Copy Number Variations*
Developmental Disabilities / genetics*
Evidence-Based Medicine / methods*
Gene Dosage
Genome, Human
Humans
Intellectual Disability / genetics*
Grant Support
ID/Acronym/Agency:
HD064525/HD/NICHD NIH HHS; MH074090/MH/NIMH NIH HHS; MH080129/MH/NIMH NIH HHS; MH083722/MH/NIMH NIH HHS; R01 MH074090/MH/NIMH NIH HHS; R01 MH080129/MH/NIMH NIH HHS; R01 MH083722/MH/NIMH NIH HHS; RC2 HD064525/HD/NICHD NIH HHS
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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