DNA diagnosis of Prader-Willi and Angelman syndromes with the probe PW71 (D15S63).

Previously, 158 nuclear families with probands suspected of having either Prader Willi (PWS) or Angelman syndrome (AS) were analyzed with polymorphic DNA markers from the 15q11-13 region. These cases have been re-evaluated with the probe PW71 (D15S63), which detects parent-of-origin-specific alleles after digestion with a methylation-sensitive restriction enzyme (HpaII). Application of PW71 to DNA samples isolated from leucocytes, confirmed the deletions and uniparental disomies detected earlier by marker analysis, and resolved 50% of the previously uninformative (n = 18) cases. PW71 and restriction fragment length polymorphism analysis indicated that, in all resolved cases, disomies of the 15q11-13 region were present. The use of PW71 increased the percentage of disomies detected in our PWS and AS patient groups. Almost 50% of our PWS patients and 17% of the AS patients showed a disomy of maternal or paternal origin, respectively. DNA of first trimester chorionic villi and of fibroblast cultures was not suitable for analysis with PW71 because of different methylation patterns. The application of PW71 is recommended for the diagnosis of the PWS and AS, with respect to DNA samples from blood.