Figure 3

Molecular and cytogenetic data for patient 99.30. A. Genotyping with STS markers reveals evidence for an interchromosomal exchange leading to the formation of the der(15). Several STS in the proximal region between BP2-BP3 show only a single maternal allele, while distal to GABRB3 a biallelic maternal contribution is apparent. This region coincides with the area of increased dosage shown by array CGH (B). The array CGH data show tetrasomy of the region from BP1 that extends midway between BP2 and BP3. The distal end of this region through BP4 shows an increase in dosage to the hexasomy range. The interval between BP4 and BP5 is consistent with terasomy. The BP positions are indicated and the box indicates control probes. The positions of the clones used for FISH are highlighted. C-G. Metaphase FISH showing the der(15) chromosome indicated multiple signals for probes within the hexasomic region. Green signals are the centromeric probe pcm15. The BAC clones are indicated in red. H. Confirmation of hexasomy for clone AC127522 by interphase FISH with pcm15 (green) clone AC127522 (red). I. Schematic of the duplication chromosome for patient 99.30. The der(15) appears to have small satellites on each end. The der(15) extends to BP5 on each end but includes an two copies of an internally duplicated segment involving the distal portion of the BP2-BP3 interval and all of the BP3-BP4 interval indicated by the hatched yellow and green segments on the diagram. The position and orientation of the internally duplicated segment are not clearly defined but appear to be asymmetrically located within the der(15) based on the FISH data. In combination with two normal chromosome 15 homologs, this leads to hexasomy for the involved segments.