DNA methylation analysis with respect to prenatal diagnosis of the Angelman and Prader-Willi syndromes and imprinting

The Angelman (AS) and Prader-Willi syndromes (PWS) are clinically distinct neurobehavioural syndromes resulting from loss of maternal (AS) or paternal contributions (PWS) of imprinted genes within the chromosomal 15q11-q13 re gion. The molecular diagnosis of both syndromes can be made by a variety of techniques, including DNA methylation, DNA polymorphism and molecular cyto genetic analyses. DNA methylation analysis at three major loci (ZNF127, PW7 1 and 5' SNRPN) has been successfully used for the postnatal diagnosis of A S and PWS. Methylation analysis, in contrast to other techniques, can relia bly be used to diagnose all three major molecular classes (deletion, unipar ental disomy and imprinting mutation) of PWS, and three of the four major c lasses of AS. In this study we demonstrate that methylation analysis can al so be successfully used in prenatal diagnosis, by examining specimens obtai ned from amniocentesis and chorionic villus sampling. Correct prenatal diag noses were obtained in 24 out of 24 samples using the 5' SNRPN locus; 4 out of 15 using the ZNF127 locus; and 10 out of 18 using the PW71 locus. There fore, our data indicate that although the DNA methylation imprints of ZNF12 7 and 5' SNRPN arise in the germline and are present in brain, only 5' SNRP N maintains the imprint in tissues suitable for the prenatal diagnosis of A S and PWS. Copyright (C) 2000 John Wiley & Sons, Ltd.