Mosaic Down syndrome with a marker: Molecular cytogenetic characterization of the marker chromosome

Down syndrome is a complex disorder characterized by well defined and distinctive phenotypic features. Approximately 2–3% of all live-born Down individuals are mosaics. Here we report a boy with suspected Down syndrome showing mosaicism for two different cell lines where one cell line is unexpected. The cytogenetic analysis by G-banding revealed a karyotype of 47 XY+21 [20]/46,X+marker [30]. Further, molecular cytogenetic analysis with spectral karyotyping identified the marker as a derivative of Y chromosome. The delineation of Y chromosomal DNA was done by quantitative real-time PCR and aneuploidy detection by quantitative fluorescence PCR. The Y-short tandem repeats typing was performed to estimate the variation in quantity as well as to find out the extent of deletion on Y chromosome using STR markers. Fluorescence in situ hybridization using Y centromeric probe was also performed to confirm the origin of the Y marker. Further fine mapping of the marker was carried out with three bacterial artificial chromosome clones RP11-20H21, RP11-375P13, RP11-71M14, which defined the hypothetical position of the deletion. In our study we defined the extent of deletion of the marker chromosome and also discussed it in relation with mosaicism. This is the first report of mosaic Down syndrome combined with a second de novo mosaic marker derived from the Y chromosome.

► We report a patient with mosaic DS and a marker. ► We identified the marker as a derivative of Y chromosome and delineated it. ► Mosaicism was an advantage in this case as he had no phenotypic features of DS and due to the presence of Y in 40% of his cell lines his genitalia was normal. ► To the best of out knowledge this is the first patient of mosaic DS combined with a second denovo mosaic marker derived from the Y chromosome.