Reanalysis of Chromosomal Microarray Data Using a Smaller Copy Number Variant Call Threshold Identifies Four Cases...

Chromosomal microarray (CMA) is a highly accurate and established method for detecting copy number variations (CNVs) in clinical genetic testing. CNVs are important etiological factors for disorders such as intellectual disability, developmental delay, and multiple congenital anomalies. Recently developed analytical methods have facilitated the identification of smaller CNVs. Therefore, reanalyzing CMA data using a smaller CNV calling threshold may yield useful information. However, this method was left to the discretion of each institution.

We reanalyzed the CMA data of 131 patients using a smaller CNV call threshold: 50 kb 50 probes for gain and 25 kb 25 probes for loss. We interpreted the reanalyzed CNVs based on the most recently available information. In the reanalysis, we filtered the data using the Clinical Genome Resource dosage sensitivity gene list as an index to quickly and efficiently check morbid genes.

The number of copy number loss was approximately 20 times greater, and copy number gain was approximately three times greater compared to those in the previous analysis. We detected new likely pathogenic CNVs in four participants: a 236.5 kb loss within ARID1B, a 50.6 kb loss including EHMT1, a 46.5 kb loss including EHMT1, and an 89.1 kb loss within the FOXP1 gene.

The method employed in this study is simple and effective for CMA data reanalysis using a smaller CNV call threshold. Thus, this method is efficient for both ongoing and repeated analyses. This study may stimulate further discussion of reanalysis methodology in clinical laboratories.