A QF-PCR system to detect chromosome 13 aneuploidy from as few as ten cells

Complete and partial trisomies of chromosome 13 are characterized by abnormal fetal development and birth defects. Despite the severe abnormalities associated with trisomy 13, some couples elect not to undergo invasive prenatal diagnosis (PND) due to the 0.5%-1.0% risk of pregnancy loss. As a result, current studies are focusing on refining non-invasive prenatal diagnostic techniques, such as screening fetal cells isolated from maternal blood or cervical smears. As these techniques only provide a limited number of cells for analysis, any progress in this field depends on the development of a highly sensitive genetic screening strategy. We have developed a quantitative fluorescent PCR (QF-PCR) system capable of detecting chromosome 13 aneuploidy from as few as 10 cells. The system was further validated by screening 13 amniocyte samples, three of which had been diagnosed by FISH as having chromosomal abnormalities involving chromosome 13. In all cases, the QF-PCR results were concordant with those obtained using FISH. The high reliability (99%) and accuracy (96%) of the QF-PCR system at the 10 cell level makes this technique ideal for use in non-invasive PND.