University of Worcester Worcester Research and Publications

Genotype-phenotype Correlations in Darier Disease - a Focus on the Neuropsychiatric Phenotype

Gordon-Smith, Katherine ORCID:, Green, E., Grozeva, D., Tavadia, S., Craddock, N. and Jones, Lisa ORCID: (2018) Genotype-phenotype Correlations in Darier Disease - a Focus on the Neuropsychiatric Phenotype. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 177 (8). pp. 717-726. ISSN Print: 1552-4841 Online: 1552-485X

Genotype-phenotype correlations in Darier disease- focus on neuropsychiatric phenotype_ NPG-18-0049 FINAL ACCEPTED VERSION ALL.pdf - Accepted Version

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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 (PA)) 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=0.011). 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=0.032).
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.

Item Type: Article
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Uncontrolled Discrete Keywords: Darier disease, neuropsychiatric features, genotype-phenotype correlations
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: College of Health, Life and Environmental Sciences > School of Allied Health and Community
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Depositing User: Katherine Gordon-Smith
Date Deposited: 26 Sep 2018 12:22
Last Modified: 09 Jul 2020 11:14

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