Formation of supernumerary euchromatic short arm isochromosomes: Parent and cell stage of origin in new cases and review of the literature

In order to get insight in the formation of isochromosomes we analysed diff erent supernumerary euchromatic short arm isochromosomes for the parent and cell stage of origin. After cytogenetic detection and confirmation by fluo rescence-in-situ hybridization we performed short tandem repeat typing in a child with i(9p), three with i(12p) and three with i(18p). The extra chrom osomes were monocentric in each case, the i(9p) and i(12p) constitutions we re found in mosaic with normal cell lines. Our results and those of other g roups indicate a strong role of maternal meiosis in isochromosome formation : in one i(8p), 4 out of 5 i(9p), 7 out of 12 i(12p) and 18 out of 23 i(18p ) families a maternal meiotic nondisjunction had occurred prior to the cent romere misdivision. For chromosome 18, the majority of isochromosomes origi nated from a maternal meiosis II error (16/18). For the other tetrasomic co nstitutions the isochromosomes could be delineated from paternal as well as from maternal origin, the short tandem repeat typing patterns being consis tent with meiotic or mitotic cell stages of formation. Thus, independently of the chromosomal origin, in the majority of cases with additional euchrom atic isochromosomes maternal meiosis nondisjunction is the initial step fol lowed by centromeric misdivision. Postzygotic nondisjunction as suggested p reviously due to mosaics observed in tetrasomies 9p and 12p seems to be of minor importance; The observed origin of isochromosomes 18 corresponds to t hat of trisomy 18, where the majority of cases can be delineated from mater nal meiosis II errors.