Identification Of Novel ATP2A2 Gene Mutations In Patients With Darier's Disease

Background Darier's disease (DD, Darier-White disease, keratosis follicularis; OMIM 124200) is a genetic skin disorder first reported in the year 1889 by Darier and White independently. It is a rare autosomal dominant disease, affecting both sexes and all ethnic groups, with a prevalence ranging from 1/30,000 to 1/100,000. The typical clinical presentation includes keratotic papules predominately in seborrheic areas, (comprising the scalp, forehead, retroauricular folds, upper arms, front and back of the central trunk, and flexures), palmoplantar pits, and distinctive nail abnormalities,with histological acantholysis and dyskeratosis.Onset of Darier's disease is usually around puberty with complete penetrance but the phenotype is variable. Mild patients may have sparsely scattered keratotic papules or subtle nail changes, whereas severe patients present verrucous plaques or malodorous hypertrophic flexural disease. In a few families, neuropsychiatric abnormalities such as mild mental retardation and epilepsy have been reported. The mutations responsible for DD have been identified in the ATP2A2 gene on chromosome 12q23-24.1. This gene encodes the sarco/endoplasmic reticulum Ca2+ ATPase type 2 isoform (SERCA2), which transports Ca2+ from the cytosol into the endoplasmic reticulum lumen and plays a pivotal role in intracellular calcium signaling. To date, at least 140 mutations in the ATP2A2 gene have been identified as the genetic basis of DD, and no apparent relation between genotype/phenotype has emerged.Objective To confirm the presence of SERCA2 mutations in Chinese DD patients and to get more information for a relationship between genotype and phenotype. Methods (1) All 21 exons including intron-exon boundaries were amplified by polymerase chain reaction (PCR) using published primers, then we sequence the ATP2A2 gene in 3 Chinese Families and 2 Sporadic Patients with DD. (2) We searched...