Determination of sensitivity and specificity of a novel gene dosage assay for prenatal screening of trisomy 21 syndrome.

Abstract : OBJECTIVE: To compare the gene dosage results achieved by a novel multiplex quantitative assay with cytogenetic and quantitative fluorescent polymerase chain reaction (QF-PCR) analysis for prenatal screening of trisomy 21 syndrome on corresponding fetal samples. DESIGN AND METHODS: Fetal samples (n=134) were collected from pregnant women considered high risk for having trisomy 21 affected fetus. Cytogenetic analysis and QF-PCR were performed. Then, the relative gene dosage of DSCAM and DYRK1A2 genes was determined on corresponding samples using comparative delta cycle of threshold (ΔC(T)) method. RESULTS: The mean gene dosage ratio was 1.55 ± 0.11 (95% CI:1.51-1.58) in trisomy 21 cases and 1.01 ± 0.12 (95% CI:0.98-1.03) in normal samples (p value<0.001). The results were in agreement to the results of cytogenetic and QF-PCR analysis with the overall specificity of 0.96 (95% CI:0.91-0.98) and the sensitivity of 0.80 (95% CI:0.49-0.94). CONCLUSIONS: This gene dosage assay is appropriate for the screening of high risk pregnant women and is readily amenable to automation.