The paradox of Prader-Willi syndrome revisited: Making sense of the phenotype.
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Holland, A., Manning, K., & Whittington, J. (2022). The paradox of Prader-Willi syndrome revisited: Making sense of the phenotype.. EBioMedicine, 78 (103952), 103952. https://doi.org/10.1016/j.ebiom.2022.103952
Prader-Willi syndrome arises as a consequence of absent paternal copies of maternally imprinted genes at 15q11-13. Such gender-of-origin imprinted genes are expressed in the brain and also in mammalian placenta where paternally expressed imprinted genes drive foetal nutritional demand. We hypothesise that the PWS phenotype is the result of the genotype impacting two pathways: first, directly on brain development and secondly, on placental nutritional pathways that results in its down-regulation and relative foetal starvation. The early PWS phenotype establishes the basis for the later characteristic phenotype. Hyperphagia. and other phenotypic characteristics arise as a consequence of impaired hypothalamic development. Hypothalamic feeding pathways become set in a state indicative of starvation, with a high satiety threshold and a dysfunctional neurophysiological state due to incorrect representations of reward needs, based on inputs that indicate a false requirement for food. Our hypotheses, if confirmed, would lead to novel and effective interventions.
Foetal nutritional pathways, Gender specific genomic imprinting, Hyperphagia, Prader-Wlli syndrome, Animals, Brain, Female, Genotype, Humans, Mammals, Phenotype, Placenta, Prader-Willi Syndrome, Pregnancy
This paper didn't require funding but we have acknowledged charitable funding for our Prader-Willi Syndrome research
Sam�s Research Foundation (via Prism the Gift Fund) (unknown)
External DOI: https://doi.org/10.1016/j.ebiom.2022.103952
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337583
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/
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