30. Dynamic mosaicism of ring chromosomes as characterized by multiple cytogenetic methods: a ring 13 and ring 21 with discordant results between microarray, karyotype, and FISH

Abstract

Ring chromosomes exhibit complex mitotic behavior with “dynamic mosaicism” resulting in complex and even discordant findings when studied by different methods. Here we present two cases of ring chromosomes identified in liveborn infants, one ring chromosome 13 [r(13)] and one ring chromosome 21 [r(21)]. In both cases, chromosomal microarray analysis identified terminal deletions, consistent with unbalanced rings, as well as mosaic gain across the remainder of the chromosome, suggestive of a sub-population having multiple copies or a double ring. The r(21) array showed an 8.1 Mb terminal deletion encompassing 21q22.2q22.3, and low-level mosaic gain of the remainder of the chromosome estimated at 12%. The r(13) case showed more complex array findings with multiple rearrangements at the breakpoint junctions, including an 11.6 Mb terminal loss of 13q33.1q34 and interstitial gains spanning 5.4 Mb of 13q32.1q33.1, and mosaic gain of the remainder of the chromosome estimated at 20%. In both cases, chromosome analyses confirmed the presence of a ring chromosome; however, clones with double rings or multiple copies of the ring were not found. Instead, monosomic cell populations were present, consistent with loss of the ring. Further characterization of the r(13) by interphase FISH on a direct (uncultured) specimen detected the monosomy 13 clone consistent with karyotype studies but no evidence of gain of 13. Interestingly, CMA performed prenatally showed results consistent with the presence of ring 13 and mosaic monosomy 13, rather than the gain of 13 observed postnatally. These findings demonstrate not only that the characterization of ring chromosomes can lead to different results when examined by different methods, but also when sampling different tissues. Complex array findings suggestive of ring chromosomes warrant additional follow-up to visualize the abnormalities and identify subpopulations masked by dynamic mosaicism that may have implications for prognosis and counseling.