Genomic microarrays in mental retardation: a practical workflow for diagnostic applications.
David A Koolen1, Rolph Pfundt, Nicole de Leeuw
1Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Human Mutation
|December 17, 2008
Summary
Interpreting copy number variants (CNVs) in diagnosing unexplained mental retardation is challenging. This study presents a workflow to assess CNV clinical significance, yielding a 9.1% diagnostic rate in a patient cohort.
Area of Science:
- Genetics
- Clinical Diagnostics
Background:
- Microarray-based copy number analysis is used in clinical practice for diagnosing unexplained mental retardation.
- Interpreting submicroscopic copy number variants (CNVs) is difficult due to their presence in the general population.
Purpose of the Study:
- To introduce and discuss a workflow for assessing the clinical significance of CNVs in routine diagnostics.
- To evaluate the diagnostic yield of this workflow in patients with unexplained mental retardation.
Main Methods:
- A genome-wide tiling-resolution DNA microarray was used.
- A workflow was applied to a cohort of 386 patients and 978 patients from literature data.
- Clinical significance of identified CNVs was assessed.
Main Results:
- In the cohort of 386 patients, 25 copy number losses, 9 copy number gains, and 1 mosaic numerical chromosome aberration were identified.
- The diagnostic yield of clinically significant CNVs in the cohort was 9.1%.
- Across 1,364 total analyses (cohort + literature), 11.2% revealed clinically significant CNVs.
Conclusions:
- The developed workflow aids in assessing the clinical significance of CNVs.
- The overall diagnostic yield of clinically significant CNVs in individuals with unexplained mental retardation is approximately 11.2%.
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