<unk>  is caused by gain-of-function mutations in the gene PIK3CD, which stands for phosphatidylinositol 3-kinase, catalytic, delta. PIK3CD maps to human chromosome 1p36.2 and encodes the p110δ catalytic PI(3)K subunit. The p110δ subunit is a protein of 1,044 amino acids that is predominantly expressed in leukocytes and plays a role in adaptive immunity. PI(3)K enzymes are activated by a variety of cell surface receptors including antigen receptors on lymphocytes. Once activated, they phosphorylate inositol lipids in the cell membrane, which triggers additional downstream signaling events. A variant of<unk>  can all be caused by heterozygous splice site mutation in PIK3R1, which encodes the p85α, p55α, and p50α regulatory PI3K subunits. These patients suffer from recurrent sinopulmonary infections and lymphoproliferation, exhibit hyperactive PI3K signaling, and have prominent expansion and skewing of peripheral blood CD8+ T cells toward terminally differentiated, senescent effector cells with short telomeres. Figure 1: p110δ protein domains; vertical red lines indicate positions of substitution mutations. ABD, adaptor-binding domain; RDB, Ras-binding domain. P110δ contains at least five domains (figure 1): adaptor-binding domain, a Ras GTPase-binding domain, a PI(3)K-type C2 domain, helical domain, and a kinase domain. Mutations have been identified in multiple domains, although there seems to be a recurrent transition mutation (G>A causing E1021K) in the C lobe of the kinase domain, leading to constitutive activation of enzyme function. Specific p110δ mutants cause stronger binding to membranes and relieve inhibition of the kinase by regulatory proteins. These changes appear to affect the immune system through over activating the downstream mTOR pathway. Inheritance<unk>  is inherited in an autosomal dominant manner. This means one only needs a single abnormal gene from his/her parents to have<unk> . Of the two copies of PIK3CD each person carries, the abnormal PIK3CD gene dominates despite the fact that the matching PIK3CD gene from the other parent is normal. Additionally, dominant inheritance means most families with<unk>  have affected relatives in each generation on the side of the family with the mutation. An alternative type of PIK3CD mutation is called de novo, which means that the mutation was not inherited from the parents but rather spontaneously arose in the patient. Children of a parent who carries a PIK3CD mutation have a 50% chance of inheriting the mutation. In a family, each child’s risk of inheriting the mutated PIK3CD gene is independent of whether or not other siblings have the mutation. For example, if the first three children in a family have the mutation, the next child has the same 50% risk of inheriting the mutation. Children who do not inherit the abnormal gene will not develop<unk>  or pass on the mutation. The variant of<unk>  due to mutations in PIK3R1 is also inherited in an autosomal dominant manner.
PASLI disease
TRIANGLE disease
BENTA disease
Weber–Christian disease
Marchiafava–Bignami disease
Degos disease
Ruijs-Aalfs syndrome
Brill–Zinsser disease