Show simple item record

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

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.

dc.format.extent717 - 726en
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.journalAmerican Journal of Medical Genetics Part B: Neuropsychiatric Geneticsen
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/School of Biomedical Sciences
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
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
dc.rights.embargoperiodNot knownen
rioxxterms.typeJournal Article/Reviewen

Files in this item


This item appears in the following Collection(s)

Show simple item record

All items in PEARL are protected by copyright law.
Author manuscripts deposited to comply with open access mandates are made available in accordance with publisher policies. Please cite only the published version using the details provided on the item record or document. In the absence of an open licence (e.g. Creative Commons), permissions for further reuse of content should be sought from the publisher or author.
Theme by 
@mire NV