Genetic basis of Darier-White disease: bad pumps cause bumps.
BACKGROUND
Darier-White disease, or keratosis follicularis, is a dominantly inherited disorder characterized by brown hyperkeratotic papules and plaques in a seborrheic distribution. The genetic basis of this disorder has recently been elucidated.


OBJECTIVE
In this article, we review the history of the search for the genetic basis of Darier-White disease.


METHODS
Previous studies are reviewed in which linkage studies identified the chromosomal location of the disease gene. The methods of physical mapping of the critical gene region and the screening of candidate genes are discussed. Results of recently published data on genotype-phenotype correlation in the disorder are presented.


RESULTS
Linkage analysis in families, together with development of a physical map of the critical region was important in identifying the causative gene. Screening of candidate genes led to the discovery that mutations in ATP2A2, a gene that encodes the sarco/endoplasmic reticulum Ca(2+)-ATPase isoform 2, cause Darier-White disease. Abnormalities in the function of this calcium pump are hypothesized to interfere with cell growth and differentiation calcium-dependent processes.


CONCLUSIONS
Genetic and molecular approaches have identified the gene for Darier-White disease and lead to more questions, including "Will this information help in the search for the Hailey-Hailey disease gene?"
Bale
S J
SJ
Genetic Studies Section, LSB, National Institute of Arthritis & Musculoskeletal & Skin Disease, National Institutes of Health, Bethesda, Maryland, USA.
Toro
J R
JR
D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D004247:DNA / Q000235:genetics; D007644:Darier Disease / Q000453:epidemiology / Q000235:genetics*; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D015994:Incidence; D009154:Mutation; D016506:Pemphigus, Benign Familial / Q000235:genetics; D010641:Phenotype
D004247:DNA