Genetic basis of Darier disease in dogs - is caused by a mutation in the ATP2A2 gene, which encodes the SERCA2 (sarcoplasmic/endoplasmic reticulum calcium ATPase 2) protein. In an Irish Terrier case, a heterozygous SINE insertion mutation near exon 15 of ATP2A2 causes aberrant splicing, leading to reduced functional protein (haploinsufficiency). It is inherited as an autosomal dominant disorder.
Pathophysiology - ATP2A2 mutations disrupt calcium regulation in keratinocytes, affecting desmosome structure and function, which are critical for cell adhesion in the epidermis. This results in epidermal hyperplasia, acantholysis (loss of cohesion between keratinocytes), and dyskeratosis. The disease manifests with impaired skin integrity and abnormal keratinocyte adhesion.
Clinical Features - Dogs typically show skin lesions before six months of age. Lesions include well-demarcated crusted plaques, ulcerative nodules, and keratotic erosions. A novel feature in affected dogs, not previously reported in humans, is the development of multiple infundibular cysts in the dermis and subcutis. These cysts are lined with squamous epithelium exhibiting suprabasal acantholysis, consistent with the pathologic changes seen in Darier disease. Lesions commonly occur on ears and other skin areas and may be painful and pruritic.
Management and Prognosis - Lesions may be successfully treated with repeated laser ablation or surgical excision of nodules. Monitoring is necessary as new cystic or crusted nodular lesions may develop over time. Secondary infections may require medical treatment alongside lesion management.
Why This Matters to Breeders and Vets - Understanding the genetic cause helps confirm diagnosis and differentiate from other acantholytic skin diseases such as Hailey-Hailey disease. Genetic testing can identify carriers and affected dogs to inform breeding decisions and prevent propagation of the disorder. Veterinarians need to recognize and manage this disease effectively to improve animals’ quality of life.