DETECTION OF ABERRANT DNA METHYLATION IN UNIQUE PRADER-WILLI-SYNDROMEPATIENTS AND ITS DIAGNOSTIC IMPLICATIONS

Most patients with Prader-Willi syndrome have a deletion of 15q11-13 o r maternal uniparental disomy for chromosome 15. The shortest region o f deletion overlap is presently defined by the gene for the small nucl ear ribonucleoprotein N (SNRPN). We have investigated the integrity of SNRPN as well as the methylation status of D15S63 (PW71) in two patie nts with apparently normal chromosomes 15 of biparental origin. SNRPN is normal in one patient and deleted in the other one. Both patients a re intact at the D15S63 locus, but have an abnormal methylation patter n. These results suggest that a DNA sequence close to SNRPN determines the methylation status of D15S63 and that the methylation test does n ot only detect the common deletions and uniparental disomy, but other rare lesions as well.