CARD11 – Immunodeficiency 11B with Atopic Dermatitis

Immunodeficiency 11B with atopic dermatitis is an autosomal dominant primary immunodeficiency characterized by recurrent infections, periodic fever, and eczematoid dermatitis. In a Chinese patient, a de novo heterozygous missense variant c.2324C>T (p.Ser775Leu) in CARD11 was identified by trio whole-exome sequencing and validated by Sanger sequencing (PMID:39414811). This variant is absent in both parents and population databases, confirming its de novo status. Functional assays—luciferase reporter, co-immunoprecipitation, and RNA sequencing—demonstrated a dominant-negative effect on wild-type CARD11, suppressing NF-κB activation and downstream transcription (PMID:39414811). No additional affected relatives were reported, and no conflicting evidence has been described.

Integration of genetic and functional data yields limited clinical validity for immunodeficiency 11B with atopic dermatitis due to a single proband but strong mechanistic concordance. Identification of c.2324C>T (p.Ser775Leu) supports molecular diagnosis and genetic counseling. Key Take-home: Dominant-negative CARD11 variants, exemplified by c.2324C>T (p.Ser775Leu), cause autosomal dominant immunodeficiency 11B with atopic dermatitis via NF-κB inhibition, underscoring the utility of CARD11 testing in early diagnosis.

References

• Scientific Reports • 2024 • A new-disease-causing dominant-negative variant in CARD11 gene in a Chinese case with recurrent fever. PMID:39414811

Evidence Based Scoring (AI generated)