Disomic homozygosity in 21-trisomic cells: a mechanism responsible for transient myeloproliferative syndrome

Abstract

Nine patients with transient myeloproliferative syndrome (TMS) with or without Down syndrome (DS) phenotype were studied cytogenetically, particularly with regard to the origin of trisomy 21. Of six DS patients, five had standard trisomy 21 and one a mosaic consisting of 21-tetrasomic, trisomic and disomic cell lines. The other three non-DS patients were mosaics with both 21-trisomic and -disomic cell lines. In all nine patients, the leukemoid cells in TMS stage were largely or exclusively composed of trisomy or tetrasomy 21, an indication that the additional chromosome(s) 21 plays an important role in the occurrence of TMS. Sequential Q- and R-banding analysis of heteromorphisms demonstrated that all these patients had a duplication of a chromosome 21, as revealed by an "aab" pattern, regardless of DS or normal phenotype or parental origin of the extra chromosome 21. Irrespective of the possibility of recombination, the "aa" chromosomes are homozygous, i.e. show disomic homozygosity: this may in turn result in the duplication of a gene that controls the proliferation of the myelogenous cells, thereby leading to TMS.