Origin of extra chromosome 21 in 343 families: cytogenetic and molecular approaches

As the knowledge of parental origin and meiotic stage of nondisjunction is the prerequisite to evaluation of the possible etiological factors in trisomy 21, we have examined 343 families with at least one Down syndrome child. Of these, 322 were primary trisomies, including 24 mosaics, and 21 were structural rearrangements. This study was carried out by analysing chromosome 21 cytogenetic heteromorphisms and molecular RFLPs. In our study first maternal meiotic nondisjunction (75.3%) is the most common mechanism leading to primary trisomies. In the 24 mosaic cases, the most frequent error occurred at the first meiotic division (83%). The origin of structural rearrangements was maternal in 15 of 21 cases. Trisomy 21q21q was due to an isochromosome, and not to a translocation.