8517

IKBKG

AMCBX1|FIP-3|FIP3|Fip3p|IKK-gamma|IP|IP1|IP2|IPD2|NEMO;inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma;IKBKG;inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma

I-kappa-B kinase subunit gamma|IKKAP1|IKKG|IkB kinase gamma subunit|NF-kappa-B essential modifier|NF-kappa-B essential modulator|NFkappaB essential modulator|ikB kinase subunit gamma|ikB kinase-associated protein 1|incontinentia pigmenti|inhibitor of nucl

Xq28

protein-coding

BACKGROUND: Nuclear factor-kappaB essential modulator (NEMO) deficiency is a developmental and immunological disorder. The genetic and phenotypic correlationhas been described. METHODS: We report a unique clinical presentation and the identification of a novel missense mutation in the NEMO gene in a 3-year-old boywith bacillus Calmette-Guerin (BCG) infection. RESULTS: The patient presented with fever, cervical lymphadenopathy, and abnormal anti-Epstein-Barr virus (EBV)antibody titers, suggestive of EBV-related diseases including chronic active EBVinfection, X-linked lymphoproliferative syndrome, or nasopharyngeal carcinoma. Although the biopsy specimen from a nasopharyngeal lesion was initially diagnosed as squamous cell carcinoma, this was changed to disseminated BCG infection involving the nasopharynx, multiple systemic lymph nodes, and brain. A novel mutation (designated D311E) in the NEMO gene, located in the NEMO ubiquitin-binding (NUB) domain, was identified as the underlying cause of the immunodeficiency. Impaired immune responses which are characteristic of patientswith NEMO deficiency were demonstrated. The patient underwent successful unrelated bone marrow transplantation at 4.9 years of age. CONCLUSION: This study suggests the importance of the NUB domain in host defense against mycobacteria. The unique presenting features in our patient indicate that a hypomorphic NEMO mutation can be associated with atypical pathological findings of the epithelialtissues in patients with BCG infection.