CLONING OF THE BREAKPOINTS OF A SUBMICROSCOPIC DELETION IN AN ANGELMAN SYNDROME PATIENT

The majority of cases of the two distinct disorders Prader - Willi syn drome (PWS) and Angelman syndrome (AS) result from cytogenetic deletio ns of chromosome 15q11 - q13. These deletions are exclusively of mater nal origin in AS but of paternal origin in PWS indicating that the 15q 11 - q13 region is subject to genomic imprinting. Transmission of a su bmicroscopic deletion in one three generation family resulted in AS on ly upon maternal transmission of the deletion with no clinical phenoty pe associated with paternal transmission (1,2). The breakpoint of this submicroscopic deletion has been cloned and sequenced. This is the fi rst deletion junction from the AS/PWS region which has been so charact erized. The nucleotide sequence of the deletion junction revealed a 19 bp insertion of unknown origin with no evidence of repetitive element s. A probe from the proximal deletion breakpoint, PB11, lies within th e currently defined minimum region of deletion overlap in PWS, which c ontains the SNRPN and D15S63 loci. Our results suggest that the imprin ted gene(s) responsible for the PWS phenotype are proximal of pB11 in this deletion overlap region.