A novel heterozygous missense variant in a CADINS patient.

BACKGROUND

-associated atopy with dominant interference of NF-κB signaling (CADINS) is developed as a result of heterozygous loss-of-function variants in that function as strong dominant-negative alleles. In lymphocytes, encodes a scaffold protein that links activation of the antigen receptor with downstream signaling. Patients with CADINS generally experience severe atopic dermatitis, asthma, recurrent pneumonia and other upper respiratory tract infections, skin infections, and allergies to a variety of dietary and environmental antigens. Additionally, patients experience elevated levels of serum IgE, but low to normal levels of other immunoglobulin types.

OBJECTIVE

We performed genetic diagnosis of a patient of nonconsanguineous descent presenting at 11 years of age with severe atopic dermatitis, asthma, food allergy, skin and recurrent infections, and an extremely elevated level of serum IgE.

METHODS

We performed whole genome sequencing of samples obtained from the patient and his entire family.

RESULTS

Clinical, laboratory, genetic, and functional findings suggested CADINS. Genetic evaluation revealed a novel heterozygous missense variant (c.2913C>G, p.Cys971Trp) in the gene as the potential underlying defect. Expression of variant-stimulated constitutive NF-κB activity in T-cell lines demonstrated both loss-of-function and dominant-negative activity.

CONCLUSION

A novel germline heterozygous missense variant (c.2913C>G) in potentially leads to CADINS.