{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:49:43Z","timestamp":1791391783458,"version":"4.3.3"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Neutrophil-specific granule deficiency is an exceptionally rare autosomal recessive primary immunodeficiency caused by pathogenic variants in the CCAAT\/enhancer-binding protein epsilon (CEBPE) gene. Defective neutrophil maturation results in impaired bactericidal activity and recurrent pyogenic infections, predominantly affecting the skin and soft tissues. We describe two affected siblings from a family of four carrying a previously unreported CEBPE missense substitution in the splice region (p.K170N; c.510G&amp;gt;C). A 37-year-old woman presented with lifelong recurrent pyogenic skin infections, including abscesses, ulcerated lesions and extensive atrophic scarring involving multiple body sites. Her brother exhibited a similar phenotype complicated by recurrent osteomyelitis, pulmonary abscesses and permanent osseous deformities. Both patients had experienced recurrent infections since early childhood and had received multiple courses of antibiotics and surgical drainage procedures before the correct diagnosis was established. Peripheral blood smear demonstrated hypogranular neutrophils with bilobed nuclei, while flow cytometry revealed aberrant CD14 expression. Genetic analysis confirmed the novel CEBPE variant in both affected siblings, establishing the diagnosis of neutrophil-specific granule deficiency.<\/jats:p>","DOI":"10.3389\/fmed.2026.1957544","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:51:42Z","timestamp":1791388302000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Recurrent severe pyogenic infections revealing neutrophil-specific granule deficiency caused by a novel CEBPEsplice-region variant: a case report"],"prefix":"10.3389","volume":"13","author":[{"given":"Ruxandra","family":"Irimia","sequence":"first","affiliation":[{"name":"Department of Hematology, Emergency Hospital Prof. Dr. Agrippa Ionescu","place":["Bucharest, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onda","family":"Calugaru","sequence":"additional","affiliation":[{"name":"Department of Hematology, Institutul Clinic Fundeni","place":["Bucharest, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Maria","family":"Forsea","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Spitalul Universitar de Urgenta Elias","place":["Bucharest, Romania"]},{"name":"Universitatea de Medicina si Farmacie Carol Davila din Bucuresti","place":["Bucharest, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara Madalina","family":"Mihai","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Spitalul Universitar de Urgenta Elias","place":["Bucharest, Romania"]},{"name":"Universitatea de Medicina si Farmacie Carol Davila din Bucuresti","place":["Bucharest, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1111\/BJH.12207","article-title":"Neutrophil-specific granule deficiency","volume":"160","author":"Mcilwaine","year":"2013","journal-title":"Br J Haematol"},{"key":"B2","author":"Charles","year":"2001"},{"key":"B3","doi-asserted-by":"publisher","first-page":"80","DOI":"10.4049\/JIMMUNOL.1402222","article-title":"A novel in-frame deletion in the leucine zipper domain of C\/EBP\u03b5 leads to neutrophil-specific granule deficiency","volume":"195","author":"Wada","year":"2015","journal-title":"The Journal of Immunology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1084\/JEM.189.11.1847","article-title":"Neutrophil-specific granule deficiency results from a novel mutation with loss of function of the transcription factor CCAAT\/enhancer binding protein \u03b5","volume":"189","author":"Lekstrom-Himes","year":"1999","journal-title":"J Exp Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"3141","DOI":"10.1182\/BLOOD.V94.9.3141.421K41_3141_315","article-title":"Myeloid transcription factor C\/EBP\u025b is involved in the positive regulation of lactoferrin gene expression in neutrophils","volume":"94","author":"Verbeek","year":"1999","journal-title":"Blood"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2018.00588","article-title":"CEBPE-mutant specific granule deficiency correlates with aberrant granule organization and substantial proteome alterations in neutrophils","volume":"9","author":"Serwas","year":"2018","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1097\/00062752-200201000-00007","article-title":"Neutrophil specific granule deficiency and mutations in the gene encoding transcription factor C\/EBP\u03b5","volume":"9","author":"Gombart","year":"2002","journal-title":"Curr Opin Hematol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2561","DOI":"10.1182\/BLOOD.V97.9.2561","article-title":"Neutrophil-specific granule deficiency: homozygous recessive inheritance of a frameshift mutation in the gene encoding transcription factor CCAAT\/enhancer binding protein-\u03b5","volume":"97","author":"Gombart","year":"2001","journal-title":"Blood"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1007\/S10875-022-01304-7\/FIGURES\/7","article-title":"A novel CEBPE variant causes severe infections and profound neutropenia","volume":"42","author":"Banday","year":"2022","journal-title":"J Clin Immunol"},{"key":"B10","first-page":"413","article-title":"Lactoferrin deficiency as a consequence of a lack of specific granules in neutrophils from a patient with recurrent infections. 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