MOLECULAR DIAGNOSIS OF PRADER-WILLI-SYNDROME - PARENT-OF-ORIGIN DEPENDENT METHYLATION SITES AND NONISOTOPIC DETECTION OF (CA)(N) DINUCLEOTIDE REPEAT POLYMORPHISMS

We describe our experience in the molecular diagnosis of 22 patients s uspected of Prader-Willi syndrome (PWS) using a DNA probe PW71 (D15S63 ) which detects a parent-of origin specific methylated site in the PWS critical region. The cause of the syndrome was determined as deletion or uniparental disomy according to the segregation of (CA), dinucleot ide repeat polymorphisms of the PWS/AS region and more distal markers of chromosome 15. In 10 patients the clinical diagnosis was confirmed by this approach, 6 with paternal deletion and 4 with maternal disomy. In one patient, the aberrant methylation pattern that was detected by PW71 could not be confirmed by the segregation of (CA),, probably due to paternal microdeletion in the PWS critical region which did not in clude the loci D15S97, D15S113, GABRB3, and GABRA5. This case demonstr ates the advantage of the DNA probe PW71 in the diagnosis of PWS. (C) 1994 Wiley-Liss, Inc.