1. Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease.
- Author
-
Sakuntabhai, Anavaj, Ruiz-Perez, Victor, Carter, Simon, Jacobsen, Nick, Burge, Susan, Monk, Sarah, Smith, Melanie, Munro, Colin S., O'Donovan, Michael, Craddock, Nick, Kucherlapati, Raju, Rees, Jonathan L., Owen, Mike, Lathrop, G. Mark, Monaco, Anthony P., Strachan, Tom, and Hovnanian, Alain
- Subjects
GENETIC mutation ,KERATOSIS follicularis ,GENETICS - Abstract
Darier disease (DD) is an autosomal-dominant skin disorder characterized by loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization. Recently we constructed a 2.4-Mb, P1-derived artificial chromosome contig spanning the DD candidate region on chromosome 12q23-24.1. After screening several genes that mapped to this region, we identified mutations in the ATP2A2 gene, which encodes the sarco/endoplasmic reticulum Ca
2+ -ATPase type 2 isoform (SERCA2) and is highly expressed in keratinocytes. Thirteen mutations were identified, including frameshift deletions, in-frame deletions or insertions, splice-site mutations and non-conservative missense mutations in functional domains. Our results demonstrate that mutations in ATP2A2 cause DD and disclose a role for this pump in a Ca2+ -signalling pathway regulating cell-to-cell adhesion and differentiation of the epidermis. [ABSTRACT FROM AUTHOR]- Published
- 1999
- Full Text
- View/download PDF