Diagnosis of the Prader-Willi syndrome by proving the absence of the unmethylated PW71 DNA fragment

The Prader-Willi syndrome (PWS) is a genetic disorder which is difficult to diagnose from clinical symptoms in newborns and young children. However, it is known that in PWS a fragment within the q11-13 region of the paternally derived chromosome 15 is deleted. Recently it has been observed that the D15S63 (PW71) locus in chromosome 15q11-13 is methylated on the maternally derived chromosome, but unmethylated on the paternally derived chromosome. Based on this observation a rapid diagnostic test (the PW71 methylation test) using methylation-sensitive restriction enzymes has been developed for patients presumed to have PWS. We have studied 56 patients; 30 patients with classical features of PWS and 26 patients with only psychomotor retardation and obesity, referred to us from different parts of Sweden. Twenty-nine of the 30 classical PWS patients were found to have an absence of the unmethylated paternally derived PW71(D15S63) locus in chromosome 15q11-13. None of the patients with only obesity and psychomotor retardation had this “absence” pattern on chromosome 15q11-13. Using the PW71 methylation test on patients with PWS, a concordance of 96% was found. The PW71 methylation test is presently the method of choice for rapid diagnostic testing of patients suspected of having PWS.