Molecular characterisation of partial chromosome 21 aneuploidies by fluorescent PCR

Although trisomy of chromosome 21 is the most prevalent human genetic disor der, data from partial 21 aneuploidies are very scanty. Eight different par tial aneuploidies for chromosome 21 were characterised by fluorescence quan titative PCR. Allelic dosage analysis was performed for each patient using 25 CHLC STRs covering the entire q arm. The length of the corresponding tri somies and monosomies was ascertained for five partial trisomics and three partial monosomics. All trisomic patients carried unbalanced translocations involving chromosome 21, whereas one of the monosomic patients bore a ring chromosome 21 and another showed an interstitial deletion of chromosome 21 . The chromosomal breakpoints of two partial trisomy patients could be clea rly delimited. However, the other three trisomies involved most of the 21 q arm as three allelic doses were detected for each marker. Although these l atter patients do not show all the features of Down syndrome, genotype/phen otype correlations agree with previously reported data. The chromosomal bre akpoints observed in two partially monosomic patients helped further to def ine the region involved in different phenotypic features associated with ch romosome 21 monosomy. Telomeric material loss was also detected in a patien t bearing a ring 21 chromosome. The parental origin of the aneuploidy was a ssigned for each case, which allowed us to conclude that two of the monosom ic cases originated from de novo chromosomal rearrangements. There was no c orrelation with parental sex in contrast to trisomic patients originating f rom meiotic nondisjunction.