CEBPE gene

CEBPE (CCAAT Enhancer Binding Protein Epsilon) is a protein-coding gene located on chromosome 14q11.2. Several variants of this gene have been described.

The protein encoded by this gene is a bZIP transcription factor that can bind to certain DNA regulatory regions as a homodimer. It can also form heterodimers with the related protein CEBP-delta. The encoded protein may be important for the terminal differentiation and functional maturation of granulocyte precursor cells. Mutations in this gene have been associated with a specific deficiency in the granules of neutrophil granulocytes.

Diseases associated with CEBPE include "Immunodeficiency 108 with autoinflammation and specific granule deficiency 1 (OMIM: 260570)

Case report: Goos et al. (2019) also investigated the sisters reported by Murros and Konttinen (1974). All 4 affected sisters developed painful recurrent tongue abscesses soon after birth, which were replaced by crater-like buccal ulcers in adolescence. They frequently suffered from single-trial paronychia, which often developed with ascending lymphangitis, as well as recurrent skin wounds or abscesses. Further characteristics were delayed wound healing and a slight tendency to bleed, e.g. epistaxis. Around puberty, all 4 sisters developed recurrent episodes of high fever with abdominal pain, lasting on average 4 to 5 days and occurring every 2 to 4 weeks. Symptoms during these episodes included vomiting, myalgias, pleurisy, arthralgia, scleritis, and episcleritis. C-reactive protein and ESR were elevated during the attacks. One patient had recurrent respiratory tract infections since the age of 42. The autoinflammatory symptoms subsided somewhat after the menopause. Two of the sisters died, one at the age of 34 from ventricular fibrillation associated with rheumatic fever and endocarditis, the other at the age of 78 from complications related to Alzheimer's disease. All showed marked neutrophil hyposegmentation in the peripheral blood smear, although the primary and secondary granules were similar to controls. Goos et al. (2019) proposed the term "CEBPE-associated autoinflammation and immunologic impairment of neutrophils (CAIN)" for this disease.

1. Goos H et al. (2019) Gain-of-function CEBPE mutation causes noncanonical autoinflammatory inflammasomopathy. J Allergy Clin Immun 144: 1364-1376
2. Murros J et al. (1974) Recurrent attacks of abdominal pain and fever with familial segmentation arrest of granulocytes. Blood 43: 871-874.
3. Repo H et al. (1979) Impaired neutrophil chemotaxis in Pelger-Huet anomaly. Clin Exp Immun 36: 326-333.