Paternally derived de novo interstitial duplication of proximal 15q in a patient with developmental delay

Interstitial duplications of proximal 15q containing the Prader-Willi syndr ome/ Angelman syndrome (PWS/AS) region have been found in patients with aut ism or atypical autism, In these cases with an abnormal phenotype, the dupl ications were maternally derived. Paternal origin of the duplication has be en associated with a normal phenotype, We report on a patient who presented with nonspecific developmental delay and partial agenesis of the rostral c orpus callosum. Fluorescence in situ hybridization (FISH) studies using pro bes specific for the PWS/AS region demonstrated a double signal on one chro mosome 15, indicating the presence of an interstitial duplication of proxim al 15q involving the PWS/AS region in the patient, Parental chromosomes wer e normal with FISH studies. Methylation analysis at exon alpha of the SNRPN locus showed a maternal band at 4.2 kb and a paternal band of apparent dou ble intensity at 0.9 kb, suggestive of one copy of the maternal allele and two copies of the paternal allele in the patient. Microsatellite analysis w as informative at the GABRB3 locus in the family, which showed the inherita nce of two different paternal alleles and a maternal allele in the patient consistent with the origin of this duplication from an unequal crossing ove r between the two chromosome 15 homologs in the father. This is the first r eport of an abnormal phenotype associated with a paternally derived duplica tion of proximal 15q shown to contain the PWS/AS region by molecular techni ques. Am. J. Med. Genet, 82:294-300, 1999. (C) 1999 Wiley-Liss, Inc.