Rapid Prenatal Diagnosis of Common Numerical Chromosomal Abnormalities by High-Resolution Melting Analysis of Segmental Duplications

Abstract

Background: Rapid aneuploidy detection (RAD) methods constitute important complements to karyotyping in prenatal diagnosis. We evaluated the effectiveness of a method called high-resolution melting analysis of segmental duplications (SD-HRM) to serve as an alternative RAD method in prenatal diagnosis of common numerical chromosomal abnormalities (NCAs). Methods: We designed eight primary SD-HRM assays for the detection of chromosomes 13, 18, 21, X, and Y; 50 chorionic villus, 1105 amniotic fluid, and 395 cord blood samples were examined using these eight assays. For diagnosing samples that could not be diagnosed using primary assays, additional assays were designed for each target chromosome. Results: The success rate of eight primary SD-HRM assays ranged from 99.7% to 100%. For the distinguishable analyses, these eight assays attained high diagnostic sensitivities (100%) and specificities (99.9-100%). We differentiated 53 cases of NCAs from 1550 clinical samples; subsequent reference tests revealed that these assays attained 100% clinical sensitivity and specificity. The mosaic ratio of a 45,X/46,XX sample was also precisely calculated. Conclusions: The SD-HRM method was able to effectively detect common NCAs in 1550 prenatal samples. We propose that SD-HRM could serve as an effective alternative option to the currently used prenatal RAD methods.