Most ATP2A2 mutations are haploinsufficiency mutations, which means that only having only one functional copy of the functional gene results in a reduced level of protein expression that is not sufficient for wild type function for making enough of the coded protein for the cell to function properly. However, there is significant variability in disease severity in how the mutations are expressed even within families that have the same mutation. It is currently unclear in the current research why a reduction in SERCA2 expression/activity causes clinical symptoms restricted to the epidermis. One hypothesis that some researchers have given is that other cell types express additional “back-up” Ca2+ pumps that can compensate for the reduced function or expression of the SERCA2 protein, while skin cells rely exclusively on the SERCA2 gene for calcium sequestration, meaning only they are affected by its reduction in expression.As mentioned above, some cases of DAR result from somatic mutations to ATP2A2 in epidermal stem cells. These cases are referred to as instances of "linear" Dariers disease. Such individuals display phenotypic mosaicism, where the Dariers phenotype only affects the subset of epidermal tissue arising from the mutated progenitor cell. Somatic mutations are not inherited by the offspring of such individuals. Diagnosis
Diagnosis of Darier disease is often made by the appearance of the skin, family history, or genetic testing for the mutation in the ATP2A2 gene. However, many individuals affected by this disorder are never diagnosed, due to the mildness of symptoms in most cases.
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.