A SOMATIC ORIGIN OF HOMOLOGOUS ROBERTSONIAN TRANSLOCATIONS AND ISOCHROMOSOMES

One t(14q14q), three t(15q15q), two t(21q21q), and two t(22q22q) nonmo saic, apparently balanced, de novo Robertsonian translocation cases we re investigated with polymorphic markers to establish the origin of th e translocated chromosomes. Four cases had results indicative of an is ochromosome: one t(14q14q) case with mild mental retardation and mater nal uniparental disomy (UPD) for chromosome 14, one t(15q15q) case wit h the Prader-Willi syndrome and UPD(15), a phenotypically normal carri er of t(22q22q) with maternal UPD(22), and a phenotypically normal t(2 1q21q) case of paternal UPD(21). All UPD cases showed complete homozyg osity throughout the involved chromosome, which is supportive of a pos tmeiotic origin. In the remaining four cases, maternal and paternal in heritance of the involved chromosome was found, which unambiguously im plies a somatic origin. One t(15q15q) female had a child with a ring c hromosome 15, which was also of probable postmeiotic origin as recombi nation between grandparental haplotypes had occurred prior to ring for mation. UPD might be expected to result from de novo Robertsonian tran slocations of meiotic origin; however, all de novo homologous transloc ation cases, so far reported, with UPD of chromosomes 14, 15, 21, or 2 2 have been isochromosomes. These data provide the first direct eviden ce that nonmosaic Robertsonian translocations, as well as isochromosom es, are commonly the result of a mitotic exchange.