Mutations in the NFKBIA gene result in functional impairment of NFKB1 (164011), a master transcription factor required for normal activation of immune responses. Interruption of NFKB1 signaling results in decreased production of proinflammatory cytokines and certain interferons, rendering ... Mutations in the NFKBIA gene result in functional impairment of NFKB1 (164011), a master transcription factor required for normal activation of immune responses. Interruption of NFKB1 signaling results in decreased production of proinflammatory cytokines and certain interferons, rendering patients susceptible to infection (McDonald et al., 2007).
Courtois et al. (2003) reported a 7-year-old boy with autosomal dominant anhidrotic ectodermal dysplasia and T-cell immunodeficiency. His parents were unaffected and not related. Since 2 months of age he had chronic diarrhea, recurrent bronchopneumonitis, hepatosplenomegaly, and failure ... Courtois et al. (2003) reported a 7-year-old boy with autosomal dominant anhidrotic ectodermal dysplasia and T-cell immunodeficiency. His parents were unaffected and not related. Since 2 months of age he had chronic diarrhea, recurrent bronchopneumonitis, hepatosplenomegaly, and failure to thrive. Bone marrow transplantation was performed at 1 year of age. A diagnosis of ectodermal dysplasia with immunodeficiency was made at the age of 3 years on the basis of dry, rough skin, moderately sparse scalp hair, and conical teeth. The patient had no other overt developmental defects. Dupuis-Girod et al. (2006) reported on the successful bone marrow transplant in the patient reported by Courtois et al. (2003). At 8 years of age, the patient had total donor chimerism in his blood cells, which restored innate and adaptive immune responses. However, he continued to receive occasional immunoglobulin substitutions. Janssen et al. (2004) reported a male infant with multiple recurrent infections. Laboratory studies showed agammaglobulinemia, increased IgM, and persistent leukocytosis composed mainly of naive T cells. During the first years of life, he was noted to have conical teeth, dry skin, periorbital wrinkling, speech delay, and growth retardation. The patient's father was diagnosed with juvenile arthritis at age 6 years and was treated with corticosteroids. He had repeated infections as a teen which were managed by antibiotics. At the time of this report, he had no health complaints and had normal serum Ig and lymphocyte counts. T cells derived from the patient showed impaired proliferative responses, but those from the father were much less severely affected. Monocytes from both patients showed defective signaling. McDonald et al. (2007) reported a 10-year-old girl with a history of multiple episodes of pneumonia since 2 months of age and evidence of bronchiectasis. Physical examination showed slightly thin hair, recessed hairline, pegged teeth, and coarse skin. She was noted to be heat intolerant and unable to sweat, and was diagnosed with ectodermal dysplasia. Her parents were unaffected. Immunologic studies showed markedly increased serum IgA and low serum IgM. Serum levels of IgG and IgG subclasses were normal. She also had lymphocytosis, with normal percentages of T and B lymphocytes and natural killer cells. T-cell proliferation studies were normal. The patient had protective titers to immunization with tetanus toxoid; however, she had no specific antibody response after immunization to any of the 14 polysaccharide antigens contained in the pneumococcal polysaccharide vaccine. Stimulation studies showed defects in the production of NFKB-dependent cytokines. Lopez-Granados et al. (2008) reported a male infant with anhidrotic ectodermal dysplasia and T-cell immunodeficiency. He had failure to thrive, developed multiple infections including gastrointestinal and respiratory infections, and died at age 9 months from complications of a cord blood transplant. Skin biopsy showed absence of sweat glands, and laboratory studies showed normal serum immunoglobulin levels but impaired production of NFKB1-regulated cytokines. In vitro studies showed that the mutant NFKBIA protein inhibited NFKB signaling by functioning as a dominant negative on NFKB activity in lymphocytes and monocytes.
In a 7-year-old boy with autosomal dominant anhidrotic ectodermal dysplasia and T-cell immunodeficiency, Courtois et al. (2003) identified a heterozygous mutation in the NFKBIA gene (S32I; 164008.0001). Janssen et al. (2004) identified the S32I mutation in a father ... In a 7-year-old boy with autosomal dominant anhidrotic ectodermal dysplasia and T-cell immunodeficiency, Courtois et al. (2003) identified a heterozygous mutation in the NFKBIA gene (S32I; 164008.0001). Janssen et al. (2004) identified the S32I mutation in a father and son with the disorder. However, the father had a much less severe phenotype and was found to be mosaic for the mutation. In a patient with anhidrotic ectodermal dysplasia and immune deficiency, McDonald et al. (2007) identified a heterozygous mutation in the NFKBIA gene (164008.0002). In a male infant with anhidrotic ectodermal dysplasia and T-cell immunodeficiency, Lopez-Granados et al. (2008) identified a de novo heterozygous mutation in the NFKB1A gene (164008.0003).