Methylation-sensitive MLPA of the chromosome 15q region. Histograms show the dosage of probes located in the SNRPN and NDN promoter regions in undigested and digested DNA. In undigested DNA, both the maternal and paternal copies of the genes are visible. Because SNRPN and NDN are paternally imprinted, after digestion with the methylation-sensitive enzyme HhaI only the maternally methylated DNA sequences are amplified, indicated by the light-colored bars. In a normal subject (control), a 50% reduction in peak height is observed after digestion. Patient 1, who has an isodicentric chromosome 15, shows 4 copies of the probes in the PWS/AS region, and a twofold increase in peak height of methylated DNA sequences, corresponding to a maternal origin of the extra chromosome. Patient 2 shows no increase in amplification of methylated DNA sequences after digestion, as expected with a duplication of paternal origin. Patient 3, with an Angelman syndrome resulting from a maternal deletion of chromosome 15q11-q13, shows a 50% reduction in peak height of probes in the PWS/AS region, and absent methylated DNA peaks after digestion. Patient 4, with Angelman syndrome resulting from a paternal uniparental disomy, shows normal peak heights before digestion with HhaI, and an absence of methylated DNA peaks afterwards, indicating the presence of two paternal chromosomes.