A large number of mutant alleles of ATP2A2 have been identified in association with Dariers Disease. One study of 19 families and 6 sporadic cases found 24 specific, novel mutations associated with DAR symptoms. This study reported a loose, imperfect correlation between the severity of ATP2A2 mutations with the severity of the condition. Significant variability in disease severity between members of the same family carrying the same mutation was also reported by this study, suggesting that genetic modifiers contribute to the phenotypic penetrance of certain mutations.The mutation is inherited in an autosomal dominant pattern. This means that only one allele needs to be mutated  in order to express the trait. This also means that someone who is born to one parent with DAR has a 50% chance of inheriting the mutant allele and having the disease. Loss-of-function mutations typically display recessive inheritance while the gain-of-function or hyperactive function of proteins is characteristic of dominant mutations. The observation that only one mutated allele of the SERCA2 is sufficient to produce clinical symptoms suggests that proper “gene dosage” is necessary for maintaining Ca2+ homeostasis in cells. This means that two wild type copies of ATP2A2 are needed for proper cell function, which provides a logical basis for dominant phenotypes arising from loss-of-function alleles.
Dariers disease (DAR) is an inherited skin disorder that presents with multiple greasy, crusting, thick brown bumps that merge into patches.It is an autosomal dominant disorder discovered by French dermatologist Ferdinand-Jean Darier. Dariers is characterized by dark crusty patches on the skin that are mildly greasy and that emit a strong odor. These patches, also known as keratotic papules, keratosis follicularis, or dyskeratosis follicularis, most often appear on the scalp, forehead, upper arms, chest, back, knees, elbows, and behind the ear.Mild forms of the disease are the most common, consisting solely of skin rashes that flare up under certain conditions such as high humidity, high stress, or tight-fitting clothes. Short stature, when combined with poorly-formed fingernails that contain vertical striations, is diagnostic even for mild forms of DAR. Symptoms will usually appear in late childhood or early adulthood  between the ages of 15 to 30 years and will vary over the course of ones life. Signs and symptoms
Clinical symptoms  of the disease:Seborrhoeic areas
This is defined as areas where excess oil and sebum is released. Overall greasy or scaly skin either in the central chest and back or in the folds of the skin. Fragile or poorly formed fingernails
Nail disease leading to V-shaped nicks at the edge of the nail. Rash that covers many areas of the body
The rash is often associated with a strong unpleasant odor
The rash can be aggravated by heat, humidity, and exposure to sunlight.