We describe a patient with manifestations of the mosaic trisomy 8 syndrome and mosaicism for a minute marker chromosome. Fluorescence in situ hybridization (FISH) with a chromosome 8 probe confirmed that the marker was derived from chromosome 8. This is the smallest piece of chromosome 8 to be reported in a patient with mosaic trisomy 8 syndrome. When the clinical picture is strongly suggestive of trisomy for a specific chromosome region, we believe that FISH can be used to test markers in a guided, rather than random, fashion.

No abstract

We present a patient with bilateral retinoblastoma and developmental delay who has an abnormal male karyotype containing 47 chromosomes, including an acentric derivative chromosome 13. We postulate that the derivative 13 occurred after a break at 13q14, with the proximal portion of the chromosome forming a ring and the distal portion undergoing duplication. Thus, this patient is trisomic for 13q14-->qter. The derivative chromosome with duplicated distal portion (13q14-->qter) lacked the 13 centromere and was negative for chromosome 13 alpha-satellite DNA by low stringency FISH. Nevertheless, this chromosome is stably transmitted in lymphocytes and fibroblasts. A single primary constriction was observed at band 13q21, consistent with activation of a latent centromere (neocentromere) at this band. The neocentromere on der(13) was positive for multiple centromeric proteins, suggesting that it acts as the functional centromere. By FISH, the Rb gene was present on the normal 13, the proximally derived ring chromosome, but not on the derivative chromosome. Although there was no evidence for disruption of the Rb gene, this chromosome rearrangement most likely results in abnormal expression of the Rb gene product.

We present a patient with minor dysmorphic features and a mosaic karyotype with two different abnormal cell lines, both involving abnormalities of chromosome 18. Twenty percent of cells studied (4/20) had 46 chromosomes with a large derivative pseudoisodicentric chromosome 18. This chromosome was deleted for 18pter and duplicated for part of proximal 18p (18p11.2 based on fluorescence in situ hybridization (FISH) studies and all of 18q. The two copies of portions of chromosome 18 were fused in an inverted fashion (duplicated for 18qter->18p11.3). The smaller der(18) was present in 80% of cells studied (16/20) and had a normal q-arm, while the p-arm was missing the subtelomere region but had duplication of a part of 18p. FISH studies showed that the larger derivative 18 contained the 18q subtelomere at each end, but the 18p subtelomere was absent, consistent with fusion of two regions within 18p resulting in deletion of the subtelomeric regions. The smaller der(18) was also missing the 18p subtelomere (with normal 18q as expected). Further testing with BAC clones mapping within 18p11.2 showed that these sequences were duplicated and inverted in both of the der(18)s. These findings lead us to hypothesize that the smaller der(18) was derived from the larger, dicentric 18 following anaphase bridge formation, with breakage distal to the duplicated segment.