The paradox of Prader-Willi syndrome: a genetic model of starvation

A Holland*, J Whittington, E Hinton

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

64 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)989-991
Number of pages3
JournalLancet
Volume362
Issue number9388
Publication statusPublished - 20 Sep 2003

Structured keywords

  • Brain and Behaviour

Keywords

  • GROWTH-HORMONE
  • ACYLATED PEPTIDE
  • IMPRINTED GENES
  • GHRELIN
  • LEPTIN
  • FETAL
  • ILLNESS
  • OBESITY
  • PEOPLE
  • WOMEN

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