DNA DIAGNOSIS OF PRADER-WILLI AND ANGELMAN SYNDROMES WITH THE PROBE PW71 (D15S63)

Previously, 158 nuclear families with probands suspected of having eit her Prader Willi (PWS) or Angelman syndrome (AS) were analyzed with po lymorphic DNA markers from the 15q11-13 region. These cases have been re-evaluated with the probe PW71 (D15S63), which detects parent-of-ori gin-specific alleles after digestion with a methylation-sensitive rest riction enzyme (HpaII). Application of PW71 to DNA samples isolated fr om leucocytes, confirmed the deletions and uniparental disomies detect ed earlier by marker analysis, and resolved 50% of the previously unin formative (n = 18) cases. PW71 and restriction fragment length polymor phism 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 materna l or paternal origin, respectively. DNA of first trimester chorionic v illi and of fibroblast cultures was not suitable for analysis with PW7 1 because of different methylation patterns. The application of PW71 i s recommended for the diagnosis of the PWS and AS, with respect to DNA samples from blood.