Molecular karyotyping of 1,295 spontaneous consecutive abortions by sequential analysis with QF-PCR, HGQ-PCR and SNP-array
Spontaneous abortions, which occur in 15-20% of all pregnancies, constitute the most common human genetic disease, since most miscarriages are caused by chromosomal anomalies. In our laboratory, we devised a protocol for sequential use of quantitative fluorescent PCR (QF-PCR), homologous gene quantitative PCR (HGQ-PCR) and SNP-arrays that allows examination of numerical and structural analyses of all chromosomes in spontaneous abortions at low cost. We describe our results with 1,295 samples of fetal tissues collected consecutively after pregnancy losses. Positive signals with QF-PCR and HGQ-PCR were always confirmed using microsatellite amplification of the specific chromosome involved. Among the exams, 64.6% were abnormal. The most common anomalies were trisomies (69.5%), triploidy (13.5%) and monosomy X (9.1%). The most frequent trisomies involved the following chromosomes: 16 (23.5%), 22 (16.0%), 21 (14.1%) and 15 (10.1%). SNP array analysis permitted the diagnoses of all trisomies. Additionally, deletions and/or duplications and chromosomal mosaicism were detected by SNP-array in 23 cases. In conclusion, our sequential analysis of fetal tissues is a new, highly useful, rapid, and cost-effective approach for the diagnosis of chromosomal alterations in spontaneous abortions.