ISOCHROMOSOME 18P RESULTS FROM MATERNAL MEIOSIS-II NONDISJUNCTION

Microsatellite analysis with 13 microsatellites spread over 18p was pe rformed to determine the origin of the marker chromosome in 9 patients with additional metacentric marker chromosomes, Phenotypes and bandin g patterns suggested that the markers were isochromosomes 18p. Materna l origin was determined in all 8 cases where both parents were availab le for study. Six cases showed 3 alleles (one paternal, one maternal e ach in single and double dose) of informative markers located close to the telomere while markers close to the centromere on 18p were reduce d to homozygosity (one paternal allele in single dosage and one matern al allele presumably in triple dosage). A similar result was obtained in the patient with no parents available for examination. The other 2 patients were uninformative for maternal hetero- versus homozygosity, but at some loci the maternal band was clearly stronger than the pater nal one whereas the opposite was never observed. Trisomy 18 differs fr om trisomy 21, XXX and XXY of maternal origin through a preponderance of meiosis II versus meiosis I nondisjunction. Thus, the results of ou r study and the advanced mean maternal age at delivery of patients wit h additional i(18p) indicate that in most if not all cases the marker chromosome originates from maternal meiosis II nondisjunction immediat ely followed by isochromosome formation in one of the 2 maternal chrom osomes 18. Possible explanations of these results include a maternally imprinted gene on 18q with a lethal effect if the paternal homologue is lost and a mechanism through which nondisjunction in some cases cou ld be connected with isochromosome formation.