The 28-kb deletion spanning D15S63 is a polymorphic variant in the Ashkenazi Jewish population

D15S63 is one of the loci, on chromosome 15q11-q13, that exhibit parent-of- origin dependent methylation and that is commonly used in the diagnosis of Prader-Willi or Angelman syndromes (PWS/AS). A 28-kb deletion spanning the D15S63 locus was identified in five unrelated patients; in each of them the deletion was inherited from a normal parent. Three of the five families se gregating the deletion were reported to be of Jewish Ashkenazi ancestry, an d in the other two families the ancestral origin was unknown. To determine whether the 28-kb deletion is a benign variant, we screened for the deletio n in 137 unselected Ashkenazi individuals and in 268 patients who were refe rred for molecular diagnosis of PWS/AS, of whom 89 were Ashkenazi and 47 we re of mixed origin (Ashkenazi and non-Ashkenazi Jews). In the control group , three individuals were carriers of the deletion; among the patients, thre e were carriers, all of whom were Ashkenazi Jews. There was no significant difference between the control group and the Ashkenazi patients, indicating that the deletion is not a cause of PWS- and AS-like syndromes. The freque ncy of the 28-kb deletion in the Ashkenazi population was 1/75. Since methy lation analysis at the D15S63 locus may lead to misdiagnosis, we suggest th e use of SNRPN, either in a PCR-based assay or as a probe in Southern hybri dization, as the method of choice in the diagnosis of PWS/AS.