DIFFERENTIAL EXPRESSION OF THE NEUROENDOCRINE POLYPEPTIDE 7B2 IN HYPOTHALAMI OF PRADER-(LABHART)-WILLI SYNDROME PATIENTS

Prader-(Labhart-)Willi syndrome (PWS) is characterized by infantile hy potonia, early childhood obesity, mental deficiency, short stature, sm all hands and feet and hypogonadism. In 70% of the cases this syndrome is associated with a defect of chromosome 15 at 15q11-q13, close to t he location of the 7B2 gene (15q13-q14). The majority of the remaining PWS patients display maternal uniparental disomy on chromosome 15. Si nce the 7B2 gene products are expressed in neuroendocrine cells that a re probably affected in PWS, e.g. by a pleiotrophic influence of the n eighboring deletion, the presence of 7B2 was studied in the supraoptic and paraventricular nucleus of the hypothalamus of five subjects clin ically diagnosed as PWS patients using five antibodies against various parts of the 7B2 precursor polypeptide. Three of the five PWS patient s studied showed no reaction to the 7B2 antibody MON-102, whereas all 30 control patients did. However, one of the three MON-102 non-reactin g PWS patients reacted to other 7B2 antibodies. In conclusion, the van ishing of 7B2 gene products is not obligatory for PWS, possibly due to the variable genetic background of PWS patients. However, in most pat ients there is a clear modification of 7B2 expression, pointing to alt ered neuroendocrine functions.