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Attenuation of the Polypeptide 7B2, Prohormone Convertase PC2, and Vasopressin in the Hypothalamus of Some Prader-Willi Patients: Indications for a Processing Defect

Graduate School Neurosciences, Netherlands Institute for Brain Research, Amsterdam, The Netherlands; Clinical Research Institute of Montreal (N.G.S.), Montreal, Canada; Laboratory for Molecular Oncology, Center for Human Genetics, Flanders Interuniversity Institute for Biotechnology, University of Leuven (J.W.V.d.L., W.J.M.V.d.V.), Leuven, Belgium; and the Department of Animal Physiology, University of Nijmegen (G.J.M.M.), Nijmegen, The Netherlands

Address all correspondence and requests for reprints to: Dr. B. A. Th. F. Gabreëls, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam ZO, The Netherlands. E-mail: B.Gabreels{at}nih.knaw.nl

7B2 is a neuroendocrine chaperone interacting with the prohormone convertase PC2 in the regulated secretory pathway. Its gene is located near the Prader-Willi syndrome (PWS) region on chromosome 15. In a previous study we were able to show 7B2 immunoreactivity in the supraoptic nucleus (SON) or the paraventricular nucleus (PVN) in only three of five PWS patients. Here we report that in contrast with five other PWS patients, the neurons in the hypothalamic SON and PVN of the two 7B2-immunonegative PWS patients also failed to show any reaction using two antibodies directed against processed vasopressin (VP). On the other hand, even these two cases reacted normally with five antibodies that recognize different parts of the VP precursor. This finding pointed to a processing defect. Indeed, the same patients had no PC2 immunoreactivity in the SON or PVN, whereas PC1 immunoreactivity was only slightly diminished. In conclusion, in the VP neurons of two PWS patients, greatly reduced amounts of 7B2 and PC2 are present, resulting in diminished VP precursor processing.

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