The paradox of Prader-Willi syndrome: a genetic model of starvation.
The neurodevelopmental disorder, Prader-Willi syndrome, is generally regarded as a genetic model of obesity. Although the values of some hypothalamic neuropeptides are as expected in obesity, and should result in satiety, we propose that abnormal hypothalamic pathways mean that these are ineffective. We postulate that the body incorrectly interprets the absence of satiation as starvation, and therefore, paradoxically, this syndrome should be redefined as one of starvation that manifests as obesity in a food-rich environment. Also, this syndrome is generally believed to be a contiguous gene disorder, which results from the absence of expression of the paternally derived alleles of maternally imprinted genes on chromosome 15 (15q11-13). We argue, however, that the whole phenotype can be explained by one mechanism and, by implication, the failure of expression of the paternal allele of a single maternally imprinted gene that controls energy balance. We suggest clinical and laboratory approaches to test our hypotheses.
D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics*; D005183:Failure to Thrive / Q000235:genetics; D005260:Female; D005315:Fetal Diseases / Q000235:genetics; D015870:Gene Expression; D018392:Genomic Imprinting / Q000235:genetics; D006801:Humans; D008297:Male; D008957:Models, Genetic; D009123:Muscle Hypotonia / Q000235:genetics; D009765:Obesity / Q000235:genetics; D010641:Phenotype; D011218:Prader-Willi Syndrome / Q000235:genetics*; D011247:Pregnancy; D013217:Starvation / Q000235:genetics*