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We studied four families each with three trisomy 21 conceptions. In two of the families the trisomy 21 conceptions all occurred when the mothers were under 35 years of age and in the other two families they all occurred when the mothers were over 35 years of age. Cytogenetic studies showed low level mosaic trisomy 21 in the two younger mothers, but not in the two older. In the three families tested using molecular techniques the results were consistent with the additional chromosome 21 in the trisomic conceptuses being maternally derived. Novel alleles were detected in the trisomic offspring of one of the younger mothers, demonstrating that the mother had been conceived as a trisomy with three different chromosomes 21. Therefore the multiple trisomy 21 pregnancies in the two younger mothers resulted from maternal trisomy 21 mosaicism, but may have been due to chance in the older mothers.

Cytogenetic and molecular study of four couples with multiple trisomy 21 pregnancies