DNA ANALYSIS IN PRADER-WILLI SYNDROME (PWS) WITH MATERNAL UNIPARENTAL DISOMY AND EXTRA INVERTED DUPLICATED CHROMOSOME

PWS has been associated with deletion of paternal 15q11-13 or maternal uniparental disomy of chromosome 15 (chr 15) (imprinting). We describe a boy with PWS with maternal uniparental disomy of chr 15 and an extra inverted duplicated chr 15 in 70% of the cells. The patient had a history of hypotonia and poor feeding as an infant, mental retardation, and hyperphagia. At age 13 yrs his height was 147 cm (10th%), weight 102 kg (>99th%), and growth rate 4.6 cm/yr. He had a narrow bifrental diameter and no acromicria. He was prepubertal and had right cryptorchidism. Serum LH and FSH were low. Testosterone was low and did not change with HCG stimulation. By DNA analysis, 8 polymorphic loci on the patient's chr 15 (7 in 15q11-13) were identical to the mother's and different from his unaffected brother's. Southern blot hybridization of the inverted duplicated segment indicated additional copies of 1 of 4 loci (D15S18) in the 15q11-13 region, proximal to the minimal critical PWS deletion region. Analyses of the parental origin of this segment are in progress. This patient appears to represent a new class of PWS with maternal disomy for chromosome 15 and an additional chromosome 15 derivative that does not contain the PWS critical region.