Darier’s disease (DD) is a skin disorder caused by mutations in the ATP2A2 gene. Researchers have been investigating the correlation between genotype and phenotype in DD. Understanding the genotype–phenotype relationship in DD can enhance our comprehension of the genetic background and phenotypic characteristics of the condition, as well as the relationship between its systemic and localized manifestations.

This study aimed to investigate the molecular pathogenesis of DD in a Chinese family, and to elucidate the genotype–phenotype correlation in DD by summarizing relevant literature.

Gene mutations associated with DD were screened by whole-exome sequencing and verified using Sanger sequencing. Genetic analysis assessed the potential impact of these mutations. Genotype–phenotype correlation was obtained by chi-square analysis using literature search test.

(1) A novel ATP2A2 Missense mutation, c.2560T>C (p.W854R), was identified and confirmed by Sanger sequencing. Annotation analysis with the ANNOVAR tool indicated that this mutation disrupts normal protein function and is linked to DD clinical manifestations. (2) Genotype–phenotype analysis showed a significant correlation between the prevalence of DD-related mental disorders and geographic regions (P = 0.00), but no association between mutation type and mental disorder prevalence (P = 0.324). The age of onset varied between sporadic and familial cases (P = 0.032), averaging 33 years in sporadic cases and 16 years in familial cases.

By analyzing the genotype–phenotype correlation, we aim to enhance our understanding of the genetic basis of DD. This research could improve early diagnosis, intervention, and the development of personalized long-term health management plans.