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dc.contributor.authorGordon-Smith, Ken
dc.contributor.authorGreen, Een
dc.contributor.authorGrozeva, Den
dc.contributor.authorTavadia, Sen
dc.contributor.authorCraddock, Nen
dc.contributor.authorJones, Len
dc.date.accessioned2018-10-27T08:52:34Z
dc.date.issued2018-12en
dc.identifier.issn1552-4841en
dc.identifier.urihttp://hdl.handle.net/10026.1/12658
dc.description.abstract

Darier disease (DD) is an autosomal dominant skin disorder caused by mutations in ATP2A2 encoding the sarco/endoplasmic reticulum Ca2+ ATPase Isoform 2 (SERCA2). Evidence of a population-level association between DD and psychiatric disorders suggests that mutations in ATP2A2 may have pleiotropic effects on the brain as well as skin. Evidence of genotype-phenotype relationships between ATP2A2 mutations and neuropsychiatric phenotypes would further support this suggestion. We investigated genotype-phenotype correlations between lifetime neuropsychiatric features and ATP2A2 mutation type (dichotomized into likely gene disrupting [LGD] or protein altering) in 75 unrelated individuals with DD. We also looked for evidence of clustering of mutations within SERCA2 according to neuropsychiatric features. Combining our data with the existing literature, the rate of LGD mutations was found to be significantly higher among DD cases/families with bipolar disorder, schizophrenia, or affective psychosis (p = .011). We also found a significant relationship between mutations located in the S4-M4 region of the protein and the presence of a severe neuropsychiatric phenotype (p = .032). Our findings add support to the hypothesis that Darier-causing mutations in ATP2A2 confer susceptibility to neuropsychiatric dysfunction, in particular severe psychiatric illness. This, together with evidence from research on common polymorphisms confirms ATP2A2 as a gene at which variation influences susceptibility to major psychiatric illness.

en
dc.format.extent717 - 726en
dc.language.isoenen
dc.publisherWileyen
dc.subjectDarier diseaseen
dc.subjectgenotype-phenotype correlationsen
dc.subjectneuropsychiatric featuresen
dc.titleGenotype-phenotype correlations in Darier disease: A focus on the neuropsychiatric phenotypeen
dc.typeJournal Article
plymouth.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/30345710en
plymouth.issue8en
plymouth.volume177en
plymouth.journalAmerican Journal of Medical Genetics Part B: Neuropsychiatric Geneticsen
dc.identifier.doi10.1002/ajmg.b.32679en
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/00 Groups by role
plymouth.organisational-group/Plymouth/00 Groups by role/Academics
plymouth.organisational-group/Plymouth/Faculty of Health: Medicine, Dentistry and Human Sciences
plymouth.organisational-group/Plymouth/Faculty of Health: Medicine, Dentistry and Human Sciences/School of Biomedical Sciences
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
plymouth.organisational-group/Plymouth/Research Groups
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR
dcterms.dateAccepted2018-08-01en
dc.rights.embargodate2019-10-22en
dc.identifier.eissn1552-485Xen
dc.rights.embargoperiodNot knownen
rioxxterms.versionofrecord10.1002/ajmg.b.32679en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-12en
rioxxterms.typeJournal Article/Reviewen


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