Classification of pathogenic or benign status of CNVs detected by microarray analysis

Abstract

Evaluation of: Hehir-Kwa JY, Wieskamp N, Webber C et al. Accurate distinction of pathogenic from benign CNVs in mental retardation. PLoS Comput. Biol. 6(4), e1000752 (2010).

Multiple lines of evidence indicated that microarray analysis has a better diagnostic yield of clinically significant genetic changes than do conventional methods in patients with constitutional abnormalities. However, interpretation of microarray data is complicated by the presence of both novel and recurrent copy number variants (CNVs) of unknown significance. To address this issue, Hehir-Kwa et al. described a new computational method for determining the pathogenicity between benign and mental retardation (MR)-associated CNVs among patients with MR. This study demonstrated the value of objectively prioritizing MR-associated CNVs using structural and functional genomic features in diagnostics. In this regard, we discuss an evidence-based summary of how to classify pathogenic or benign status of a CNV in clinical genetics and advocate that there is a need for algorithmic adjustment between constitutional cytogenetic and prenatal diagnosis settings.

Keywords::

• CNV
• mental retardation
• microarray analysis
• pathogenic
• postnatal
• prenatal

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.