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dc.contributor.authorBaker, Kateen
dc.contributor.authorScerif, Gaiaen
dc.contributor.authorAstle, Duncanen
dc.contributor.authorFletcher, Paulen
dc.contributor.authorRaymond, Lucyen
dc.date.accessioned2015-09-02T14:31:06Z
dc.date.available2015-09-02T14:31:06Z
dc.date.issued2015-02-27en
dc.identifier.citationBaker et al. Journal of Neurodevelopmental Disorders (2015), 7:8. doi:10.1186/s11689-015-9105-xen
dc.identifier.issn1866-1947
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/250435
dc.description.abstractBackground Rare pathogenic variants in membrane-associated guanylate kinase (MAGUK) genes cause intellectual disability (ID) and have recently been associated with neuropsychiatric risk in the non-ID population. However, it is not known whether risk for psychiatric symptoms amongst individuals with ID due to MAGUK gene mutations is higher than expected for the degree of general intellectual impairment, nor whether specific cognitive differences are associated with disruption to this gene functional network. Methods This study addresses these two questions via behavioural questionnaires and cognitive testing, applying quantitative methods previously validated in populations with ID. We compared males with X-linked ID caused by mutations in three MAGUK genes (PAK3, DLG3, OPHN1; n = 9) to males with ID caused by mutations in other X chromosome genes (n = 17). Non-parametric and parametric analyses were applied as appropriate to data. Results Groups did not differ in age, global cognitive impairment, adaptive function or epilepsy prevalence. However, individuals with MAGUK gene mutations demonstrated significantly higher psychopathology risks, comprising elevated total problem behaviours, prominent hyperactivity and elevated scores on an autism screening checklist. Despite these overt difficulties, individuals in the MAGUK group performed more accurately than expected for age and intelligence quotient (IQ) on computerised tests of visual attention, convergent with mouse models of MAGUK loss-of-function. Conclusions Our findings support a role for MAGUK genes in influencing cognitive parameters relevant to psychiatric risk. In addition to establishing clear patterns of impairment for this group, our findings highlight the importance of careful phenotyping after genetic diagnosis, showing that gene functional network disruptions can be associated with specific psychopathological risks and cognitive differences within the context of ID.
dc.description.sponsorshipWe thank all study participants and their families for extensive contributions to this project. This study was funded by the Academy of Medical Sciences/Wellcome Trust via a Starter Grant for Clinical Lecturers to KB. KB is funded by a National Institute for Health Research Academic Clinical Lectureship. GS is funded by a Wellcome Trust project grant and a James S. McDonnell Foundation Understanding Human Cognition Scholar Award. DEA is funded by an MRC UK intramural programme (MC-A0606-5PQ41). FLR is funded by the National Institute for Health Research (Cambridge Biomedical Research Centre).
dc.languageEnglishen
dc.language.isoenen
dc.publisherBioMed Central
dc.rightsAttribution 2.0 UK: England & Wales*
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/*
dc.subjectMAGUKen
dc.subjectIntellectual disabilityen
dc.subjectGeneticsen
dc.subjectCognitionen
dc.subjectPsychiatric disordersen
dc.subjectDLG3en
dc.titlePsychopathology and cognitive performance in individuals with membrane-associated guanylate kinase mutations: a functional network phenotyping studyen
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s11689-015-9105-xen
prism.number8en
prism.publicationDate2015en
prism.publicationNameJournal of Neurodevelopmental Disordersen
prism.volume7en
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.funderNIHR
dc.rioxxterms.funderMRC
dc.rioxxterms.projectidMC-A0606-5PQ41
dcterms.dateAccepted2015-02-07en
rioxxterms.versionofrecord10.1186/s11689-015-9105-xen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-02-27en
dc.contributor.orcidBaker, Kate [0000-0003-2986-0584]
dc.contributor.orcidAstle, Duncan [0000-0002-7042-5392]
dc.contributor.orcidFletcher, Paul [0000-0001-8257-1517]
dc.contributor.orcidRaymond, Lucy [0000-0003-2652-3355]
dc.identifier.eissn1866-1955
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMEDICAL RESEARCH COUNCIL (G0001354)
pubs.funder-project-idWellcome Trust (100140/Z/12/Z)
pubs.funder-project-idWellcome Trust (095692/Z/11/Z)


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales