DNA METHYLATION BASED TESTING OF 450 PATIENTS SUSPECTED OF HAVING PRADER-WILLI-SYNDROME

Using a test based on parent of origin specific DNA methylation at the D15S63 (PW71) locus, we studied 385 patients (aged 1 to 36 years) for diagnostic confirmation of Prader-Willi syndrome (PWS) and 65 infants (aged 0 to 12 months) with severe hypotonia of unknown cause. Fifty e ight of 385 patients were examined personally; 28/58 patients had PWS and lacked the paternal PW71 band and 30/58 patients, who did not have PWS, had a normal methylation pattern. In five of these patients, a d ifferential diagnosis was made (Ohdo-like blepharophimosis syndrome, A lstrom syndrome, Cohen syndrome, Bardet-Biedl syndrome, and pseudohypo parathyroidism). A total of 327/385 blood samples was sent to us from outside. The test confirmed the diagnosis of PWS in 112/327 patients. Most of the other 215 patients lacked the major diagnostic criteria su ch as neonatal hypotonia, feeding problems, characteristic facies, and hypogenitalism. On the other hand, 29/65 hypotonic infants tested pos itive for PWS. We conclude that the PW71 methylation test detects most , if not all, patients with typical PWS and that PWS is often not reco gnised in infants and wrongly suspected in obese and mentally retarded patients.