A VARIETY OF GENETIC MECHANISMS ARE ASSOCIATED WITH THE PRADER-WILLI-SYNDROME

An extensive set of chromosome 15 DNA polymorphisms and densitometric analysis with four markers mapping to the Prader-Willi chromosome regi on (PWCR) of chromosome 15 have been used to characterize a cohort of 30 subjects with classical Prader-Willi syndrome (PWS). Molecular anal ysis enabled the classification of the PWS subjects into four groups: (A) 18 subjects (60%) had deletions of paternal 15q11-13 involving a c ommon set of DNA markers. Two subjects had differently sized deletions , one larger and one smaller than the other cases. (B) Eight (27%) had maternal uniparental disomy for chromosome 15. (C) One (3%) had a mar ker chromosome carrying an extra copy of the PWCR. The marker chromoso me was demonstrated to be of paternal origin and the two intact chromo somes were maternally derived. This case represents an apparent except ion to the generally held view that PWS is associated with an absence of paternally inherited gene(s) located in the PWCR. (D) The remaining three cases (10%) had none of the above abnormalities. This last subg roup of patients has not previously been well characterized but could represent limited deletions not detectable with the markers used or ab normalities in the imprinting process. These cases represent potential ly valuable resources to elucidate more precisely the fundamental diso rders responsible for PWS. (C) 1994 Wiley-Liss, Inc.