<unk>  is caused by loss-of-function mutations in the gene TPP2, which stands for tripeptidyl peptidase II. TPP2 maps to human chromosome 13q32-q33, has 32 exons, and encodes for a 1249 amino acid protein. The genetic model for this disease is loss-of-function. This means that for people with<unk> , the gene TPP2 is unable to produce protein or produce functional protein. Functionally, TPPII has a key role in recycling amino acids, which are protein building blocks, a fundamental cellular process. Although the body can use alternative amino acid recycling pathways to compensate for loss of TPPII, the up-regulation of alternative pathways can cause new cellular abnormalities in itself with subsequent effects on glycolysis, adaptive immunity, and innate immunity. Consequently, individuals without functioning TPPII have severe disease. Inheritance<unk>  is inherited in an autosomal recessive manner. In autosomal recessive inheritance, two copies of an abnormal gene must be present in order for the disease to develop. Typically, this means both parents of an affected child silently carry one abnormal gene. This also means this also explains why reported cases of<unk>  have involved consanguinity or geographically isolated communities. Parents of a child with<unk>  have a 25% chance of having another affected child with each pregnancy. This risk is independent of prior children’s status. For example, if the first two children in a family are affected, the next child has the same 25% risk of inheriting the mutation. All affected individuals have two abnormal copies of TPP2. Children who inherit only one abnormal copy of TPP2 will not develop<unk>  although they may have affected children, particularly if they marry within the family.
TRIANGLE disease
BENTA disease
Pogosta disease
Darier's disease
Freiberg disease
Tornwaldt's disease
Haff disease
Degos disease