Differential expression of the neuroendocrine polypeptide 7B2 in hypothalami of Prader-(Labhart)-Willi syndrome patients.
Prader-(Labhart-)Willi syndrome (PWS) is characterized by infantile hypotonia, early childhood obesity, mental deficiency, short stature, small 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 the location of the 7B2 gene (15q13-q14). The majority of the remaining PWS patients display maternal uniparental disomy on chromosome 15. Since the 7B2 gene products are expressed in neuroendocrine cells that are probably affected in PWS, e.g. by a pleiotrophic influence of the neighboring deletion, the presence of 7B2 was studied in the supraoptic and paraventricular nucleus of the hypothalamus of five subjects clinically diagnosed as PWS patients using five antibodies against various parts of the 7B2 precursor polypeptide. Three of the five PWS patients studied showed no reaction to the 7B2 antibody MON-102, whereas all 30 control patients did. However, one of the three MON-102 non-reacting PWS patients reacted to other 7B2 antibodies. In conclusion, the vanishing of 7B2 gene products is not obligatory for PWS, possibly due to the variable genetic background of PWS patients. However, in most patients there is a clear modification of 7B2 expression, pointing to altered neuroendocrine functions.
Gabreëls
B A
BA
Graduate School of Neurosciences/Netherlands Institute for Brain Research, Amsterdam-Zuidoost.
Swaab
D F
DF
Seidah
N G
NG
van Duijnhoven
H L
HL
Martens
G J
GJ
van Leeuwen
F W
FW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D051859:Neuroendocrine Secretory Protein 7B2; D009490:Neurosecretory Systems / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D010865:Pilot Projects; D010907:Pituitary Hormones / Q000096:biosynthesis*; D011218:Prader-Willi Syndrome / Q000378:metabolism*; D013495:Supraoptic Nucleus / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D051859:Neuroendocrine Secretory Protein 7B2; D010907:Pituitary Hormones; C497678:SCG5 protein, human