Screening fetal losses for monosomy X with a simple PCR-based procedure

To screen for monosomy X in spontaneous fetal losses we explored a simple m olecular strategy based on loss of heterozygosity at highly polymorphic X-l inked loci. We developed a multiplex fluorescent procedure that allows the simultaneous amplification of five dinucleotide repeat polymorphisms in a l arge low-recombination region in the long arm of the X chromosome. Analysis was performed by computer-assisted laser densitometry. We did not find any instances of homozygosity at all five loci in 30 normal females tested, no r among 37 women whose typing data were retrieved from the Fondation Jean D ausset - CEPH genotype database. In addition, all cases of monosomy X previ ously diagnosed by conventional cytogenetics presented the anticipated loss of heterozygosity at all loci. We studied 19 spontaneously aborted female fetuses and we found four samples homozygous for the five loci (21%), in go od agreement with the expected rate of monosomy X in first trimester sponta neous abortions. We conclude that the loci have high diversity and high eff iciency in PCR-amplification and that our multiplex procedure constitutes a simple and useful molecular screening test for monosomy X in abortions and stillbirths.