Cloning of the breakpoints of a submicroscopic deletion in an Angelman syndrome patient

The majority of cases of the two distinct disorders Prader–Willisyndrome (PWS) and Angelman syndrome (AS) result from cytogeneticdeletions of chromosome 15q11–q13. These deletions areexclusively of maternal origin in AS but of paternal originin PWS indicating that the 15q11–q13 region is subjectto genomic imprinting. Transmission of a submicroscopic deletionin one three generation family resulted in AS only upon maternaltransmission of the deletion with no clinical phenotype associatedwith paternal transmission (1, 2). The breakpoint of this submicroscopicdeletion has been cloned and sequenced. This is the first deletionjunction from the AS/PWS region which has been so characterized.The nucleotide sequence of the deletion junction revealed a19 bp insertion of unknown origin with no evidence of repetitiveelements. A probe from the proximal deletion breakpoint, PB11,lies within the currently defined minimum region of deletionoverlap in PWS, which contains the SNRPN and D15S63 locl. Ourresults suggest that the imprinted gene(s) responsible for thePWS phenotype are proximal of pB11 in this deletion overlapregion.