DNA studies of mono- and pseudodicentric isochromosomes 18q.

The description of isochromosomes 18 has so far mainly been by cytogenetic studies and based on identical banding pattern of the two arms. However, only molecular techniques are capable to distinguish an isochromosome from a translocation, whole arm or reciprocal, between two chromosomes 18. We have used 23 PCR-based DNA polymorphisms to determine the parental origin and mechanisms of formation in four patients with isochromosomes 18q and to demonstrate that they were consistent with true isochromosomes. Three of the probands were liveborn children with clinical features characteristic of Edwards syndrome, one proband was a fetus diagnosed at prenatal diagnosis. In one case the isochromosome was monocentric with two identical q arms of maternal origin, formed by misdivision of the centromere and loss of p arm material. Another monocentric case had 47 chromosomes with isochromosomes i(18p) and i(18q) formed by maternal postzygotic centromeric misdivision and segregation of both isochromosomes, or by meiosis II centromeric misdivision and nondisjunction (without recombination in meiosis I). In two cases, the isochromosomes were dicentric with genetically identical arms composed of a part of the short and the whole long arm of chromosome 18 of paternal origin. The formation of the fused chromosomes can be explained by postzygotic exchange of sister chromatids on the short arm of chromosome 18, followed by breakage and U-shape reunion of sister chromatids.