Noninvasive Prenatal Screening for 22q11.2 Deletion/Duplication Syndrome Using multiplex dPCR

Abstract Background 22q11.2 deletion/duplication syndrome has a high incidence in prenatal fetuses and cause variety of severe abnormalities. At present, screening for 22q11.2 deletion/duplication syndrome in fetuses is difficult because of the lack of effective targeted programs. Methods In this study, six detection sites and their corresponding probes were designed in the 22q11.2 recurrent region, and a dPCR assay for noninvasive screening of 22q11.2 deletion/duplication syndrome was established. A total of 106 plasma samples from pregnant women (including ten samples with fetal 22q11.2 deletion/duplication syndrome) were blindly tested to evaluate the sensitivity and specificity of the assay. Results DNA with different sizes of 22q11.2 deletion/duplication was detected by dPCR, indicating that these probes and detection site designs were reasonable and effective. In the retrospective clinical samples of the cffDNA assay, eight out of ten samples of pregnant women with 22q11.2 deletion/duplication were detected, and accurate regional localization was achieved. Of the 96 normal samples, 93 were confirmed. Receiver operating characteristic curves were used to assess the cut-off values and AUC for these samples. The sensitivity, specificity, and positive as well as negative predictive values were 80%, 96.9%, 72.7%, and 97.9%, respectively. Conclusion The cffDNA assay based on dPCR technology for noninvasive detection of 22q11.2 recurrent copy number variants in fetuses can detect most affected cases, including smaller but relatively common nested deletions, with a low false-positive rate. It has the potential to provide an efficient and simple dPCR assay for noninvasive screening of 22q11.2 deletion/duplication syndrome.