Background: Darier's disease (DD) is an autosomal dominant skin disorder characterized by abnormal keratinization and acantholysis. Pathogenic mutations in the ATP2A2 gene encoding SERCA2, a calcium pump of the sarco/endoplasmic reticulum, have recently been identified. Objectives: To identify mutations of the ATP2A2 gene in Taiwanese patients with DD. Methods: Mutation analysis of genomic DNA was performed on five families with DD and two sporadic cases. All 21 exons and the flanking intron boundaries were amplified and followed by direct sequencing. Restriction fragment analysis or direct sequencing in each family and in normal controls further verified the mutations. Results: Mutations in the functional domains of the ATP2A2 gene were identified and verified in all seven pedigrees. They consisted of four mis-sense mutations (R131Q, P680L, G703S, G807R), one altered splice-site mutation (2980 + 5insA) and one frameshift deletion mutation (1457-1458delAG). Of these, R131Q, which was reported twice previously, was detected in two unrelated families. The remaining five were novel mutations. Conclusions: Six pathogenic mutations in the ATP2A2 gene were identified in seven Taiwanese DD pedigrees. The results confirmed that most mutations in the ATP2A2 gene are private and of the mis-sense type.
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