MODIFICATION OF 15Q11-Q13 DNA METHYLATION IMPRINTS IN UNIQUE ANGELMANAND PRADER-WILLI PATIENTS

The clearest example of genomic imprinting in humans comes from studie s of the Angelman (AS) and Prader - Willi (PWS) syndromes. Although th ese are clinically distinct disorders, both typically result from a lo ss of the same chromosomal region, 15q11 - q13. AS usually results fro m either a maternal deletion of this region, or paternal uniparental d isomy (UPD; both chromosomes 15 inherited from the father). PWS result s from paternal deletion of 15q11 - q13 or maternal UPD of chromosome 15. We have recently described a parent-specific DNA methylation impri nt in a gene at the D15S9 locus (new gene symbol, ZNF127), within the 15q11 - q13 region, that identifies AS and PWS patients with either a deletion or UPD. Here we describe an AS sibship and three PWS patients in which chromosome 15 rearrangements alter the methylation state at ZNF127, even though this locus is not directly involved in the rearran gement. Parent-specific DNA methylation imprints are also altered at Z NF127 and D15S63 (another locus with a parent-specific methylation imp rint) in an AS sibship which have no detectable deletion or UPD of chr omosome 15. These unique patients may provide insight into the imprint ing process that occurs in proximal chromosome 15 in humans.