Several recent studies have suggested the presence of mosaicism for a deletion, detected by fluorescence in situ hybridization (FISH), within chromosome 15q11-q13 in Prader-Willi syndrome (PWS) [Mowery-Rushton et al., 1996;Malzac et al., 1998;Golden et al., 1999]. However, the evidence supporting mosaicism in such cases is nondefinitive, and biological considerations suggest that the putative deletion mosaicism in several of these cases is unlikely. Here, I briefly discuss rationale to take into account for chromosomal analyses in PWS and suggest experiments that can prove or disprove the mosaicism hypothesis in such cases. The consideration of whether mosaicism is present has important diagnostic and biological implications for PWS and may also be relevant to other chromosomal deletion syndromes in humans.
Mosaicism appears to be unlikely in three of the cases presented by Mowery-Rushton et al. [1996], none of whom fulfill diagnostic criteria for PWS. In the first case (PW1), a deletion is claimed in 30% of peripheral blood leukocytes for three of four probes, but not for the D15S10 locus located between flanking deleted loci. Although complex rearrangements are occasionally seen in human genetics, the presence of a discontinuous deletion in mosaic state represents two rare or previously unseen events in PWS, and thus the proposed events appear unlikely and should have been verified by additional studies (see below).
Similarly, two patients (PW4 and PW10) are suggested to be deleted at D15S10 only, in βΌ15% of cells, and not at the other three loci studied within 15q11-q13 [Mowery-Rushton et al., 1996]. To explain these cases, one hypothesis suggested by the authors proposes that critical genes for PWS may be located near D15S10. However, D15S10 is located at the telomeric end of the UBE3A gene in a region that is associated with Angelman syndrome (AS) and not with PWS [