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dc.contributor.authorHolland, Anthony
dc.contributor.authorManning, Katie
dc.contributor.authorWhittington, Joyce
dc.date.accessioned2022-05-27T23:31:06Z
dc.date.available2022-05-27T23:31:06Z
dc.date.issued2022-04
dc.identifier.issn2352-3964
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/337583
dc.description.abstractPrader-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.
dc.description.sponsorshipThis paper didn't require funding but we have acknowledged charitable funding for our Prader-Willi Syndrome research
dc.format.mediumPrint-Electronic
dc.publisherElsevier BV
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectFoetal nutritional pathways
dc.subjectGender specific genomic imprinting
dc.subjectHyperphagia
dc.subjectPrader-Wlli syndrome
dc.subjectAnimals
dc.subjectBrain
dc.subjectFemale
dc.subjectGenotype
dc.subjectHumans
dc.subjectMammals
dc.subjectPhenotype
dc.subjectPlacenta
dc.subjectPrader-Willi Syndrome
dc.subjectPregnancy
dc.titleThe paradox of Prader-Willi syndrome revisited: Making sense of the phenotype.
dc.typeArticle
dc.publisher.departmentDepartment of Psychiatry
dc.date.updated2022-05-27T13:01:14Z
prism.number103952
prism.publicationDate2022
prism.publicationNameEBioMedicine
prism.startingPage103952
prism.volume78
dc.identifier.doi10.17863/CAM.84992
dcterms.dateAccepted2022-03-07
rioxxterms.versionofrecord10.1016/j.ebiom.2022.103952
rioxxterms.versionVoR
dc.contributor.orcidHolland, Anthony [0000-0003-4107-130X]
dc.identifier.eissn2352-3964
rioxxterms.typeJournal Article/Review
pubs.funder-project-idSam�s Research Foundation (via Prism the Gift Fund) (unknown)
cam.issuedOnline2022-03-19
cam.depositDate2022-05-27
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International