Representation of the CARD11 protein showing the general domain structure and two different gain-of-function missense mutations associated with<unk>  located just upstream of the coiled-coil (CC) domain<unk>  is caused by germline-encoded gain-of-function mutations in the gene CARD11. This is a 138 kB gene mapping to chromosome 7p22 with 26 exons encoding a 1,154 amino acid protein. The CARD11 protein (also known as CARMA1) is a scaffolding protein required for NF-κB activation in both B and T lymphocytes. Gain-of-function mutations drive constitutive NF-κB activation in both types of cells. Most mutations are localized within or just upstream of the coiled-coil domain (exons 4-9) of the protein. Patient phenotypes also suggest that B cell differentiation might be partially impaired in<unk> , contributing to a low percentage of class-switched and memory B cells. Germline gain-of-function mutations in CARD11 manifest a less severe illness than loss-of-function mutations seen in CARD11 deficiency ( OMIM #615206), an autosomal recessive condition manifesting in severe combined immunodeficiency. The gain-of-function CARD11 mutations associated with<unk>  may also predispose patients to B cell malignancy. Importantly, overactive NF-κB is frequently associated with B cell malignancy and, specifically, somatic gain-of-function CARD11 mutations are seen frequently in diffuse large B cell lymphoma (DLBCL). However, most<unk>  patients present with polyclonal B cell accumulation with no evidence of oligoclonal or monoclonal populations (i.e. malignancy). These mutations do not appear to be associated with T cell malignancies. Inheritance This disorder is inherited in an autosomal dominant manner. Autosomal refers to the fact that every person has two CARD11 alleles, one inherited from each parent. This is in contrast to sex-linked chromosomes. Dominant means that the abnormal allele dominates the matching, normal allele. Only one of the two copies (alleles) of CARD11 needs to be abnormal for a person to have<unk> .<unk>  can also arise spontaneously in a patient as the result of a de novo mutations in CARD11, which means that the mutation was not inherited from the parents. In this case the patient could still pass on the mutation to his/her children. Children of a parent who carries a CARD11 mutation have a 50% chance of inheriting the mutation. In a family, each child’s risk of inheriting the mutated CARD11 allele is independent of whether or not other siblings inherited the mutation. For example, if the first four 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 mutation will not develop<unk>  nor pass it on to their children.
BENTA disease
Degos disease
Pogosta disease
TRIANGLE disease
Bahima disease
Fox–Fordyce disease
Cruveilhier–Baumgarten disease
Borna disease