Methylation analysis with probe PW71 (D15S63) is an established procedure to test patients suspected of having Prader-Willi syndrome or Angelman syndrome. Using this test, we have identified a 28-kb deletion spanning D15S63 in five independent families. Sequence analysis revealed identical breakpoints in all the families. The haplotype data are compatible with a common ancestral origin of the deletion in at least two families. The deletion was not found in 1, 000 unrelated controls. Although the deletion maps within the imprinting-center region, neither maternal nor paternal inheritance of the deletion appears to affect imprinting in proximal 15q. We conclude that the deletion is a rare neutral variant that can lead to false-positive results in the PW71-methylation test.

. Imprinting on human chromosome 15q11-q13 is controlled by a bipartite imprinting center (IC) that maps to the SNRPN locus. Deletions of the IC result in an imprinting defect and Prader-Willi syndrome or Angelman syndrome (AS). We have now identified a 5-kb IC deletion in an English AS patient (AS- LO ); this represents the smallest microdeletion found in AS and narrows down the shortest region of deletion overlap to 880 bp.

A long-range restriction map encompassing the APC (adenomatous polyposis coli) gene has been constructed. The map includes 35 DNA markers and consists of two segments of 10 and 2.5 Mb. Published genetic markers have been connected using additional, nonpolymorphic DNA probes. The map clarifies marker order and allows comparison of physical and genetic data.