BALANCED TRANSLOCATION 46,XY,T(2-15)(Q37.2-Q11.2) ASSOCIATED WITH ATYPICAL PRADER-WILLI-SYNDROME

The lack of normally active paternal genes in 15q11-q13, as an outcome of either a paternal deletion or maternal disomy, accounts for >95% o f all patients with Prader-Willi syndrome. Other mechanisms, including imprinting mutations and unbalanced translocations involving pat 15q1 1-q13, have been described elsewhere. In this study, we present a pati ent with a rare balanced, de novo translocation-46,XY,t(2;15)(q37.2;q1 1.2)-involving breakage within the Prader-Willi/Angelman syndrome regi on of the paternal homologue, without an apparent deletion, The patien t demonstrated several manifestations of the Prader-Willi syndrome but was clinically atypical, Cytogenetic and molecular studies of this ca se demonstrated the translocation breakpoint to be between SNRPN and I PW with mRNA expression of SNRPN and PAR-5 but absence of IPW and PAR- 1 expression. These results suggest that disruption of either IPW expr ession or a nearby gene by an upstream break may contribute to the Pra der-Willi syndrome phenotype and that expression of SNRPN or other ups tream genes is responsible for other aspects of the classical Prader-W illi syndrome phenotype.