Genetic epidemiology of Darier's disease: a population study in the west of Scotland

Summary Background Darier's disease has a world‐wide distribution, but estimates of prevalence have varied. The discovery that the disease is due to mutations in ATP2A2 provides the opportunity to study the genetic epidemiology of the disease in localized populations. Objectives To survey the prevalence of Darier's disease in the west of Scotland and look for founder effects in this population. Methods We ascertained cases of Darier's disease in the west of Scotland and used genealogy and mutational analysis to seek common ancestry. Results Seventy‐eight current cases were identified, giving a prevalence of ∼1 : 30 000. While 63 cases gave a history of Darier's disease in previous generations, conventional genealogy identified only two pairs of two family groups with common ancestry within the last 180 years. Eleven patients (14%; three of whom had in total four affected children) had probable de novo mutations. Causative mutations in ATP2A2 have been identified in 11 of 15 pedigrees screened for mutation, but no two share the same mutation. Conclusions High estimates of prevalence are likely to be due to intensive ascertainment, rather than founder effects. Darier's disease is likely to be more common than has been recognized in other populations.