MOLECULAR ANALYSIS OF MOSAICISM FOR 2 DIFFERENT DE-NOVO ACROCENTRIC REARRANGEMENTS DEMONSTRATES DIVERSITY IN ROBERTSONIAN TRANSLOCATION FORMATION

Robertsonian translocations (ROBs) involving chromosome 21 occur in ab out 5% of individuals with Down syndrome, ROBs are the most common chr omosomal rearrangements in humans and are formed through whole arm exc hanges of any two acrocentric chromosomes, The de novo formation of RO Bs occurs at exceptionally high rates. The present case concerns a chi ld with mosaic Down syndrome who has two cell lines that contain two d ifferent de novo ROBs: 45,XX,rob(14;21) (q10;q10) and 46,XX,rea(21;21) (q10;q10),+21. To elucidate the mechanisms by which the rearrangement s formed, somatic cell hybrids were constructed to allow the parental origins of the chromosomes involved in the ROBs to be distinguished, T he analysis of the hybrids showed that the rob(14q21q) must have forme d postzygotically because it contained a maternal chromosome 14 and a paternal chromosome 21. Furthermore, hybrid analysis of the rea(21q21q ) demonstrated two copies of the same chromosome from the mother and t hus, by definition, was an isochromosome [i(21q)], All free-lying chro mosomes 21 isolated in hybrids were of maternal origin, These chromoso mes may have originated from either of the patient's cell lines. We pr esent four hypotheses for the formation of the two cell lines of this child. This case is part of an ongoing project to determine the mechan ism(s) of de novo ROB formation and the results differ from the other de novo rob(14q21q) studied in our laboratory (n = 7) in that all prev iously studied translocations were maternally derived, leading to the conclusion that most de novo rob(14q21q) occur in oogenesis, The curre nt case illustrates that ether mechanisms may contribute to ROB format ion, (C) 1998 Wiley-Liss, Inc.