Abstract: Objective: To detect the genetic mutations in 9 cases with Darier's disease (DD) by Sanger sequencing and whole exome sequencing (WES). Methods: The genomic DNA was extracted from peripheral blood of 2 patients from one family, 7 sporadic patients and 100 normal controls. Sanger sequencing was used to detect ATP2A2 pathogenic mutations in 9 DD patients. In the patients with non-mutations of ATP2A2, the whole exome sequencing (WES) was performed to search for other variants that may potentially cause this disease. Three hundred and sixty-four healthy controls were included for mutation screening. Suspected variants were confirmed by Sanger sequencing. Results: By Sanger sequencing, we found that 5 patients had ATP2A2 mutation, including 1 reported mutation and 3 new mutations. In other cases, four variants in four ATPase genes (ITPR3, ATP2B2, RYR1, and PLCB1) were identified by WES, all of which were involved in calcium signal pathway. Conclusion: In this study, four mutations in ATP2A2 gene were identified including 3 novel mutations, which broaden the spectrum of ATP2A2 mutations. Moreover, our study suggests that four ATPase gene variants may be associated with DD.

Key words: Darier's disease, ATP2A2, calcium signal pathway