Sensitivity of DCSR3/GAPDH ratio using quantitative real-time PCR in the rapid prenatal diagnosis for down syndrome.

BACKGROUND: Down syndrome, the most common birth defect, is caused by trisomy 21. The aim of this study was to investigate whether quantitative real-time PCR can be used as a sensitive technique for prenatal diagnosis of Down syndrome. METHODS: We used a quantitative real-time PCR technique to measure the gene dosage of the Down syndrome critical region (DSCR3) by calculating the ratio of DSCR3 to GAPDH using standard curves. Sex-determining region Y was simultaneously detected by real-time PCR to identify the sex of the fetus. RESULTS: The DSCR3/GAPDH ratio of the trisomy 21 fetus samples and that of normal controls was 0.72 +/- 0.34 and 0.54 +/- 0.18, respectively. CONCLUSION: In this study, there was no significant difference in the DSCR3/GAPDH ratio between the fetal and peripheral blood DNA samples of trisomy 21 fetuses and those of normal controls.

Long interspersed nuclear element-1 (LINE1)-mediated deletion of EVC, EVC2, C4orf6, and STK32B in Ellis-van Creveld syndrome with borderline intelligence.

Previous work has shown Ellis-van Creveld (EvC) patients with mutations either in both alleles of EVC or in both alleles of EVC2. We now report affected individuals with the two genes inactivated on each allele. In a consanguineous pedigree diagnosed with EvC and borderline intelligence, we detected a 520-kb homozygous deletion comprising EVC, EVC2, C4orf6, and STK32B, caused by recombination between long interspersed nuclear element-1 (LINE-1 or L1) elements. Patients homozygous for the deletion are deficient in EVC and EVC2 and have no increase in the severity of the EvC typical features. Similarly deletion carriers demonstrate absence of digenic inheritance in EvC. Further, the phenotype of these patients suggests that the EVC-STK32B deletion also leads to mild mental retardation and reveals that loss of the novel genes C4orf6 and STK32B causes at most mild mental deficit. In an EvC compound heterozygote of different ethnic origin we identified the same LINE-to-LINE rearrangement due to a different recombination event. These findings highlight the importance of L1 repetitive sequences in human genome architecture and disease.