Abstract
Approximately 15–20% of all clinically recognised pregnancies abort, most commonly between 8–12 gestational weeks. While the majority of early pregnancy losses is attributed to cytogenetic abnormalities, the aetiology of approximately 40% of early abortions remains unclear. To determine additional factors causing spontaneous abortions we retrospectively searched for uniparental disomies (UPD) in 77 cytogenetically normal diploid spontaneous abortions. In all cases an unbalanced chromosome anomaly was ruled out by cytogenetic investigation of chorionic/amniotic membranes and/or chorionic villi. For UPD screening microsatellite analyses were performed on DNA of abortion specimens and parental blood using highly polymorphic markers showing UPD in two cases. The distribution of markers analysed indicated maternal heterodisomy for chromosome 9 (UPhD(9)mat) in case 1 and paternal isodisomy for chromosome 21 (UPiD(21)pat) in case 2. The originating mechanism suggested was monosomy complementation in UPiD(21)pat and trisomy rescue in UPhD(9)mat. In the case of UPhD(9)mat purulent chorioamnionitis was noted and a distinctly growth retarded embryo of 3 cm crown-rump length showing no gross external malformations. Histological analysis in the case of UPiD(21)pat suggested a primary anlage defect. Our results indicate that less than 3% of genetically unexplained pregnancy wastage is associated with total chromosome UPD. UPD may contribute to anlage defects of human conception. Chromosome aneuploidy correction can occur in very early cleavage stages. More research, however, ought to be performed into placental mosaicism to further clarify timing and mechanisms involved in foetal UPD.
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Acknowledgements
We express our appreciation to all the couples who agreed to participate in our study, at a time of personal distress. We thank their physicians for their cooperation, particularly Dr Hoffmann, Diakonie Krankenhaus Wehrda, Marburg. The technical assistance of Maritha Lippmann (Marburg), Madeleine Skorna (Berlin) and Marga Schepens (Nijmegen) is gratefully acknowledged. We thank Dr J Köhler for critical suggestions concerning the manuscript. Large scale PCR analysis was done at the Max Delbrück-Center, Berlin. This work was supported by a grant from the Deutsche Forschungsgemeinschaft DFG (Re 429/8-1/Fr 1302/1-2).
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Fritz, B., Aslan, M., Kalscheuer, V. et al. Low incidence of UPD in spontaneous abortions beyond the 5th gestational week. Eur J Hum Genet 9, 910–916 (2001). https://doi.org/10.1038/sj.ejhg.5200741
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DOI: https://doi.org/10.1038/sj.ejhg.5200741
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