Novel ATP2A2 mutations in a large sample of individuals with Darier disease.
Darier disease (DD) is a rare autosomal dominantly inherited skin disorder caused by mutations in ATP2A2, which is expressed in both the skin and the brain and encodes for SERCA2. We have screened the coding regions of ATP2A2 in a total of 95 unrelated individuals with DD to identify the pathogenic mutations. We identified 66 potentially pathogenic mutations in ATP2A2 for 74 of the 95 individuals with DD of which 45 (68%) are thought to be novel. Forty-nine (74%) are unique to an individual and 17 (26%) were found in more than one individual or overlap with previously identified variants. The results suggest that mutations in ATP2A2 may not be as family-specific as first thought. The spectrum of mutations identified will inform understanding of the pathogenesis of DD.
MRC Center for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK. greenek@cf.ac.uk
Elaine K
EK
Green
Katherine
K
Gordon-Smith
Susan M
SM
Burge
Detelina
D
Grozeva
Colin S
CS
Munro
Sherine
S
Tavadia
Lisa
L
Jones
Nicholoas
N
Craddock
D007644:Darier Disease / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics*
D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human