Development and implementation of a new rapid aneuploidy diagnostic service within the UK National Health Service and implications for the future of prenatal diagnosis

Background Prenatal diagnosis for chromosome abnormality is routinely under taken by full karyotype analysis of chromosomes from cultured cells; pregna nt women must wait on average 13-14 days for their results. Autosomal triso mies, which account for around 80% of significant abnormalities, can be det ected by quantitative fluorescence (QF) PCR. We report on the development a nd implementation of this technique as the first such routine service withi n a diagnostic department of the UK National Health Service (NHS). Methods We designed a "one-tube test" comprising four primer pairs for poly morphic tetranucleotide repeat sequences on chromosome 21, four primer pair s for sequences on chromosome 18, three primer pairs for sequences on chrom osome 13, and one primer pair to identify the sex chromosomes. All prenatal samples received by our NHS diagnostic department between April, 2000, and April, 2001, were tested. After DNA extraction, PCR amplification was done and the products separated on a capillary-based genetic analyser; the resu lts were interpreted with dedicated software. Follow-up karyotype analysis was done on all samples. Findings 1148 amniotic fluid samples, 188 chorionic villus samples, and 37 fetal tissue samples were tested; the amplification failure rate was zero w ith our current protocol. QF-PCR results were obtained and reported on 1314 (98%) of the prenatal samples; the remaining 22 (2%) were uninformative be cause of maternal-cell contamination. One case of mosaicism in a chorionic villus sample, and two cases indicating somatic expansion of a tetranucleot ide repeat were found. No false positive or false negative results were obt ained. The mean reporting time for the last 4 months of data collection was 1.25 working days. Interpretation QF-PCR aneuploidy testing is an efficient and accurate techn ique for the detection of autosomal trisomies in prenatal samples. Implemen tation of this service has led to the rapid diagnosis of abnormalities and early reassurance for women with normal results.