SNP Shot: Genomic Insights

Generalized pustular psoriasis (GPP) is a serious type of psoriasis, a skin disease caused by irregular inflammation. Inflammation is a normal part of the immune system's defense against injury and infection. However, in GPP and other psoriasis types, this inflammation becomes uncontrolled, leading to damage of tissues and organs. People with GPP experience recurring episodes where large areas of their skin become red, inflamed, and covered with small, pus-filled blisters (pustules). These skin issues can be accompanied by symptoms like fever, severe fatigue, muscle weakness, elevated white blood cell count, and widespread inflammation throughout the body (systemic inflammation). These inflammatory episodes come and go, often triggered by factors such as infection, certain medications (starting or stopping them), menstruation, or pregnancy. However, the trigger is often unknown. Without treatment, GPP can be life-threatening.

Many individuals have only symptoms of GPP (referred to as GPP alone). However, some people develop features of psoriasis vulgaris (PV), the most common form of psoriasis, either before or after the onset of GPP. PV is characterized by red, scaly skin patches (plaques) appearing on various parts of the body.

Inheritance:

When GPP is linked to mutations in the IL36RN gene, it's typically inherited in an autosomal recessive manner. This means that both copies of the gene in each cell must have mutations for the individual to be at risk. The parents of someone with an autosomal recessive condition each carry one copy of the mutated gene. When GPP is associated with mutations in the CARD14 gene, the risk is inherited in an autosomal dominant pattern. This means that only one copy of the altered gene in each cell is enough to increase the risk of developing the disorder. In some cases, the mutation is inherited from a parent, while in other cases, it arises as a new (de novo) mutation in the gene.

Having mutations in either the IL36RN or CARD14 gene increases the risk of developing GPP, but it doesn't guarantee that the condition will develop. Not everyone with GPP has mutations in these genes, and not everyone with a mutation in these genes will develop GPP.