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Title: Neuropsychiatric phenotype in Darier's Disease
Author: Gordon-Smith, Katherine Mary
ISNI:       0000 0004 2746 9626
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2008
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Darier's Disease (DD) is a rare autosomal dominantly inherited skin disorder in which co-occurrence of neuropsychiatric abnormalities has been frequently reported by dermatologists. The disease is caused by mutations in a single gene, ATP2A2, which maps to 12q23-q24.1 and is expressed in the skin and brain. This gene encodes SERCA2 (sarco/endoplasmic reticulum Ca 2+ ATPase isoform 2), a calcium pump involved in intracellular calcium transport. This study aimed to conduct the first systematic investigation of the neuropsychiatric phenotype in DD, investigate possible genotype-phenotype correlations, and compare the neuropsychiatric features in DD individuals and their first-degree unaffected relatives. One hundred unrelated individuals with DD and 24 of their unaffected relatives were assessed using a battery of standardised neuropsychiatric measures. The relationship between the mutations detected in iheATP2A2 gene and the presence/severity of neuropsychiatric phenotypes was examined. DD individuals reported high rates of mood disorders, specifically major depression (30%), suicide attempts (13%) and suicidal thoughts (31%), and these were significantly more common in DD when compared with normative population data. Further, individuals with DD reported higher scores on measures of neuropsychiatric dysfunction than their unaffected relatives. These associations cannot be explained by psychosocial factors. Mutations found among individuals with similar neuropsychiatric phenotypes clustered in certain locations within the SERCA2b protein. Together, these findings support the hypothesis that mutations mATP2A2 confer susceptibility to neuropsychiatric dysfunction, in particular mood disorders, in individuals with DD. These findings highlight the need for assessment and recognition of psychiatric symptoms in DD. The findings may also have implications for identification of other genetic factors involved in conferring susceptibility to neuropsychiatric features in individuals without DD. Further research is needed into other neuropsychiatric phenotypes in DD and into the specific functional effects of mutations in ATP2A2 and the relationship of these to the presence of certain neuropsychiatric phenotypes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available