Detection of copy number variants using chromosomal microarray analysis for the prenatal diagnosis of congenital...

With the increasing availability of chromosomal microarray analysis (CMA) for congenital heart defect (CHD), genetic testing now faces new challenges due to results with uncertain clinical impact. Studies are needed to better define the penetrance of genetic variants. The aim of the study was to examine the association between CMA and CHDs in fetuses with normal karyotype.

This was a retrospective study of 190 fetuses with normal karyotype that underwent CMA after a diagnosis of CHD by fetal ultrasound. Invasive prenatal diagnosis was performed between January 2015 and December 2016 at the first affiliated hospital of Air Force Medical University.

Chromosomal microarray analysis detected pathogenic copy number variants (pCNVs) in 13/190 (6.84%) fetuses, likely pCNVs in 5/190 (2.63%), and variants of unknown significance (VOUS) in 14/190 (7.37%). Among those with pCNVs, none (0%) yielded a normal live birth. Among those with likely pCNVs, 2/5 (40.0%) yielded a live birth. Among the fetuses with VOUS, 10/14 (71.5%) yielded a live birth.

These results highlight the usefulness of CMA for prenatal genetic diagnosis of fetuses with CHDs and normal karyotype. In fetuses with CHD, the application of CMA could increase the detection rate of pCNVs causing CHDs. In this study, some VOUS were likely pathogenic, but additional studies are necessary to confirm these findings.