Figure 2

A-F Structure and FISH results of the mosaic inv dup(4) from case 1. 2A: a metaphase using FISH for WCP4 shows (green signals) that the extra material on 4p is indeed of intrachromosomal 4 origin. The newly interstitial sub-telomeric region in the (arrowed) inv dup (4) is poorly hybridized here, due to the presence of repetitive telomeric sequences (competitively excluded in the WCP hybridization). 2B: FISH on a metaphase from the apparently normal cell line showing a deletion of the sub-telomere probe for 4p (clone GS-36p21, shown in red) in one homologue (arrowed). The intact sub-telomere probe for 4q (clone GS-963K6 shown in green) is also demonstrated on both chromosomes. 2C: There is a sub-telomere deletion (absence of clone GS36p21 – shown in red) also in the interstitially located p-telomeric region of the (arrowed) inv dup(4). 2D: the pantelomeric probe for TTAGGG (green) is found on the 4pter of the chromosome, albeit with a missing subtelomere 4p locus, i.e. a positive TTAGGG signal is present on both (open arrows) the normal chromosome 4 and the 4p with the cryptic subtelomere deletion. In all FISH figures, chromosomes were identified by reversing the DAPI image (not shown). 2E: the pantelomeric probe (green) shows that TTAGGG repeats are found on the "new" 4pter (solid arrow) of the inv dup(4) chromosome (both normal 4 and inv dup(4) are indicated by open arrows). 2F: interstitially, there is a duplication (arrowed) of the Wolf-Hirschhorn locus (clone WHSCR in red) in the inv dup(4), confirming the inv dup structure. The CEP4 (4 centromere) control probe is shown in green.