PMID- 10441325
OWN - NLM
STAT- MEDLINE
DCOM- 20000127
LR  - 20220331
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 8
IP  - 9
DP  - 1999 Sep
TI  - ATP2A2 mutations in Darier's disease and their relationship to neuropsychiatric
      phenotypes.
PG  - 1631-6
AB  - Darier's disease (DD) is a rare, dominantly inherited disorder that affects the
      skin producing a variety of types of lesion. Close examination of lesional DD
      skin shows the presence of abnormal keratinization (epidermal differentiation)
      and acantholysis (loss of cohesion) of keratinocytes. A number of clinical
      studies have described the co-occurrence of various neurological and psychiatric 
      symptoms with DD, including mood disorders, epilepsy, mental retardation and a
      slowly progressive encephalopathy. A single locus for DD has been mapped to
      chromosome 12q23-q24.1, and a variety of missense, nonsense, frameshift and
      splicing mutations in the ATP2A2 gene have been described recently in families
      with DD. This gene encodes the sarcoplasmic/endoplasmic reticulum calcium-pumping
      ATPase SERCA2, which has a central role in intra-cellular calcium signalling. In 
      this study, we performed mutation analysis on ATP2A2 in 19 unrelated DD patients,
      of whom 10 had neuropsychiatric phenotypes. We identified and verified 17 novel
      mutations predicting conservative and non-conservative amino acid changes,
      potential premature translation terminations and potential altered splicing. Our 
      findings confirm that mutations in ATP2A2 are associated with DD. In
      neuropsychiatric cases, there was a non-random clustering of mutations in the 3' 
      end of the gene ( P = 0.01), and a predominance of the missense type (70% versus 
      38% in DD patients). This supports the hypothesis that the DD gene has
      pleiotropic effects in brain and that mutations in SERCA2 are implicated in the
      pathogenesis of neuropsychiatric disorders.
FAU - Jacobsen, N J
AU  - Jacobsen NJ
AD  - Neuropsychiatric Genetics Unit, Division of Psychological Medicine, Tenovus
      Building, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, 
      UK.
FAU - Lyons, I
AU  - Lyons I
FAU - Hoogendoorn, B
AU  - Hoogendoorn B
FAU - Burge, S
AU  - Burge S
FAU - Kwok, P Y
AU  - Kwok PY
FAU - O'Donovan, M C
AU  - O'Donovan MC
FAU - Craddock, N
AU  - Craddock N
FAU - Owen, M J
AU  - Owen MJ
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Membrane Proteins)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
SB  - IM
MH  - Adult
MH  - Calcium-Transporting ATPases/*genetics
MH  - Chromosomes, Human, Pair 12
MH  - Darier Disease/*genetics/pathology/psychology
MH  - Female
MH  - Humans
MH  - Male
MH  - Membrane Proteins/genetics
MH  - Mental Disorders/genetics
MH  - Middle Aged
MH  - *Mutation
MH  - Phenotype
MH  - Protein Structure, Secondary
MH  - Skin/*pathology
EDAT- 1999/08/11 00:00
MHDA- 1999/08/11 00:01
CRDT- 1999/08/11 00:00
PHST- 1999/08/11 00:00 [pubmed]
PHST- 1999/08/11 00:01 [medline]
PHST- 1999/08/11 00:00 [entrez]
AID - ddc193 [pii]
AID - 10.1093/hmg/8.9.1631 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1999 Sep;8(9):1631-6. doi: 10.1093/hmg/8.9.1631.