Paternal UPD15: Further Genetic and Clinical Studies in Four Angelman Syndrome Patients

Among 25 patients diagnosed with Angelman syndrome, we detected 21 with deletion and 4 with paternal uniparental disomy (UPD), 2 isodisomies originating by postzygotic error, and 1 MII nondisjunction event. The diagnosis was obtained by molecular techniques, including methylation pattern analysis of exon 1 of SNRPN and microsatellite analysis of loci within and outside the 15q11-q13 region. Most manifestations present in deletion patients are those previously reported. Comparing the clinical data from our and published UPD patients with those with deletions we observed the following: the age of diagnosis is higher in UPD group (average 7 3 ⁄12 years), microcephaly is more frequent among deletion patients, UPD children start walking earlier (average age 2 9 ⁄12 years), whereas in deletion patients the average is 4 1 ⁄2 years, epilepsy started later in UPD patients (average 5 10 ⁄12 years) than in deletion patients (average 1 11 ⁄12 years), weight above the 75th centile is reported mainly in UPD patients, complete absence of speech is more common in the deleted (88.9%) than in the UPD patients because half of the children are able to say few words. Thus, besides the abnormalities already described, the UPD patients have somewhat better verbal development, a weight above the 75th centile, and OFC in the upper normal range. Am. J. Med. Genet. 92:322-327, 2000