Prader-Willi syndrome (PWS) is caused by the disturbed expression of genes from 
the imprinted region of 15q11-q13, but the specific contributions of individual 
genes remain unknown. Most paternal PWS deletions are bracketed by recurrent 
breakpoints BP1 or BP2 and BP3. Atypical deletions are very rare. In the present 
work, we describe the molecular analysis of two patients with atypical deletions 
using microsatellite analysis, methylation-specific MLPA, and microarray CGH. A 
deletion of about 2 Mb in Patient 1 started at BP2 and ended in the middle of 
the typically deleted region within the UBE3A gene. The deletion in Patient 2 
started 1.3 Mb distal from BP2 within the C15ORF2 gene, extended over 9.5 Mb, 
and ended within the AVEN gene in proximal 15q14. In Patient 1 both deletion 
breakpoints involved repetitive regions, which precluded cloning of the junction 
and pointed to non-allelic homologous recombination as a possible mechanism of 
this rearrangement. The breakpoints in Patient 2 were sequenced, and their 
structure suggested non-homologous end joining as the most likely cause of this 
deletion. The phenotype of both patients did not depart significantly from the 
typical clinical picture of PWS, although some symptoms in Patient 2 were also 
reminiscent of the phenotype of individuals with the recently described 15q13.3 
microdeletion syndrome. Our findings support previous observations of relatively 
mild phenotypic effects resulting from deletions that extend distally from the 
PWS region and observations of the modest effects of different types of genetic 
defects on the spectrum and severity of symptoms in PWS.