{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T18:13:36Z","timestamp":1761848016532,"version":"build-2065373602"},"reference-count":15,"publisher":"Walter de Gruyter GmbH","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jpem-2025-0065_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      To describe the case of a young girl with severe congenital neutropenia caused by a homozygous variant in the Jagunal homolog 1 (\n                      <jats:italic>JAGN1<\/jats:italic>\n                      ) gene, who later developed atypical diabetes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2025-0065_abs_002\">\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      <jats:italic>JAGN1<\/jats:italic>\n                      deficiency disrupts neutrophil maturation, resulting in immunodeficiency and recurrent infections. Our patient also exhibited impaired humoral immunity, requiring immunoglobulin replacement therapy, which reduced infection frequency. Several years after the identification of her\n                      <jats:italic>JAGN1<\/jats:italic>\n                      mutation, she developed atypical insulin-dependent diabetes mellitus\u00a0\u2013\u00a0a condition not previously associated with\n                      <jats:italic>JAGN1<\/jats:italic>\n                      mutations. This novel finding suggests a potential role for\n                      <jats:italic>JAGN1<\/jats:italic>\n                      in pancreatic \u03b2-cell function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2025-0065_abs_003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This case expands the spectrum of\n                      <jats:italic>JAGN<\/jats:italic>\n                      <jats:italic>1<\/jats:italic>\n                      -related immune dysfunction and introduces a potential link between\n                      <jats:italic>JAGN1<\/jats:italic>\n                      deficiency and diabetes. We explore possible mechanisms underlying this association, highlighting the need for further research. Clinicians should consider\n                      <jats:italic>JAGN1<\/jats:italic>\n                      mutations in the differential diagnosis of combined immune and metabolic disorders.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jpem-2025-0065","type":"journal-article","created":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T07:59:01Z","timestamp":1752911941000},"page":"1217-1223","source":"Crossref","is-referenced-by-count":0,"title":["A case of\n                    <i>JAGN1<\/i>\n                    mutation presenting with atypical diabetes and immunodeficiency"],"prefix":"10.1515","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0410-8372","authenticated-orcid":false,"given":"C\u00e9line","family":"De Cuyper","sequence":"first","affiliation":[{"name":"Department of Pediatrics , 60201 Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel) , Brussels , Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8259-3329","authenticated-orcid":false,"given":"Willem","family":"Staels","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology , Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel) , Brussels , Belgium"},{"name":"Genetics, Reproduction and Development (GRAD) , Vrije Universiteit Brussel (VUB), Beta Cell Neogenesis (BENE) , Brussels , Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6056-8533","authenticated-orcid":false,"given":"Siel","family":"Daelemans","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology , Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel) , Brussels , Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8817-6139","authenticated-orcid":false,"given":"Jesse","family":"Vanbesien","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology , Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel) , Brussels , Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9136-9126","authenticated-orcid":false,"given":"Elise","family":"Nauwynck","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology , Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel) , Brussels , Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8571-0858","authenticated-orcid":false,"given":"Inge","family":"Gies","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology , Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel) , Brussels , Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"2025103018011134632_j_jpem-2025-0065_ref_001","doi-asserted-by":"crossref","unstructured":"Khandagale, A, Lazzaretto, B, Carlsson, G, Sundin, M, Shafeeq, S, R\u00f6mling, U, et al.. JAGN1 is required for fungal killing in neutrophil extracellular traps: implications for severe congenital neutropenia. J\u00a0Leukoc Biol 2018;104:1199\u2013213. https:\/\/doi.org\/10.1002\/jlb.4a0118-030rr.","DOI":"10.1002\/JLB.4A0118-030RR"},{"key":"2025103018011134632_j_jpem-2025-0065_ref_002","doi-asserted-by":"crossref","unstructured":"Klein, C. Genetic defects in severe congenital neutropenia: emerging insights into life and death of human neutrophil granulocytes. Annu Rev Immunol 2011;29:399\u2013413. https:\/\/doi.org\/10.1146\/annurev-immunol-030409-101259.","DOI":"10.1146\/annurev-immunol-030409-101259"},{"key":"2025103018011134632_j_jpem-2025-0065_ref_003","doi-asserted-by":"crossref","unstructured":"Huang, J, Xiao, Y, Xu, A, Zhou, Z. Neutrophils in type 1 diabetes. J\u00a0Diabetes Investig 2016;7:652\u201363. https:\/\/doi.org\/10.1111\/jdi.12469.","DOI":"10.1111\/jdi.12469"},{"key":"2025103018011134632_j_jpem-2025-0065_ref_004","doi-asserted-by":"crossref","unstructured":"Thomas, S, Guenther, G, Rowe, JH, Platt, CD, Shimamura, A, Levy, O, et al.. Severe congenital neutropenia due to jagunal homolog 1 (JAGN1) mutation: a case report and literature review. Front Pediatr 2023;11:1223191. https:\/\/doi.org\/10.3389\/fped.2023.1223191.","DOI":"10.3389\/fped.2023.1223191"},{"key":"2025103018011134632_j_jpem-2025-0065_ref_005","doi-asserted-by":"crossref","unstructured":"McDermott, DH, Malech, HL. JAGN1 mutations in severe congenital neutropenia. Br J Haematol 2021;192:9\u201310. https:\/\/doi.org\/10.1111\/bjh.17135.","DOI":"10.1111\/bjh.17135"},{"key":"2025103018011134632_j_jpem-2025-0065_ref_006","doi-asserted-by":"crossref","unstructured":"Hojabri, M, Farsi, Y, Jamee, M, Abolhassani, H, Khani, HHK, Karimi, A, et al.. JAGN1 mutation with distinct clinical features; two case reports and literature review. BMC Pediatr 2023;23:206. https:\/\/doi.org\/10.1186\/s12887-023-04024-y.","DOI":"10.1186\/s12887-023-04024-y"},{"key":"2025103018011134632_j_jpem-2025-0065_ref_007","doi-asserted-by":"crossref","unstructured":"Baris, S, Karakoc-Aydiner, E, Ozen, A, Delil, K, Kiykim, A, Ogulur, I, et al.. JAGN1 deficient severe congenital neutropenia: two cases from the same family. J\u00a0Clin Immunol 2015;35:339\u201343. https:\/\/doi.org\/10.1007\/s10875-015-0156-2.","DOI":"10.1007\/s10875-015-0156-2"},{"key":"2025103018011134632_j_jpem-2025-0065_ref_008","doi-asserted-by":"crossref","unstructured":"Boztug, K, J\u00e4rvinen, PM, Salzer, E, Racek, T, M\u00f6nch, S, Garncarz, W, et al.. JAGN1 deficiency causes aberrant myeloid cell homeostasis and\u00a0congenital neutropenia. Nat Genet 2014;46:1021\u20137. https:\/\/doi.org\/10.1038\/ng.3069.","DOI":"10.1038\/ng.3069"},{"key":"2025103018011134632_j_jpem-2025-0065_ref_009","doi-asserted-by":"crossref","unstructured":"Hagelkruys, A, Wirnsberger, G, Stadlmann, J, W\u00f6hner, M, Horrer, M, Vilagos, B, et al.. A crucial role for Jagunal homolog 1 in humoral immunity and antibody glycosylation in mice and humans. J\u00a0Exp Med 2021;218. https:\/\/doi.org\/10.1084\/jem.20200559.","DOI":"10.1084\/jem.20200559"},{"key":"2025103018011134632_j_jpem-2025-0065_ref_010","doi-asserted-by":"crossref","unstructured":"Smith, TD, Cunningham-Rundles, C. Detection of anti-glutamic acid decarboxylase antibodies in immunoglobulin products. J\u00a0Allergy Clin Immunol Pract 2018;6:260\u20131. https:\/\/doi.org\/10.1016\/j.jaip.2017.04.042.","DOI":"10.1016\/j.jaip.2017.04.042"},{"key":"2025103018011134632_j_jpem-2025-0065_ref_011","doi-asserted-by":"crossref","unstructured":"Nosak, C, Silva, PN, Sollazzo, P, Moon, KM, Odisho, T, Foster, LJ, et al.. Jagn1 is induced in response to ER stress and regulates proinsulin biosynthesis. PLoS One 2016;11:e0149177. https:\/\/doi.org\/10.1371\/journal.pone.0149177.","DOI":"10.1371\/journal.pone.0149177"},{"key":"2025103018011134632_j_jpem-2025-0065_ref_012","doi-asserted-by":"crossref","unstructured":"Lee, S, Cooley, L. Jagunal is required for reorganizing the endoplasmic\u00a0reticulum during Drosophila oogenesis. J\u00a0Cell Biol 2007;176:941\u201352. https:\/\/doi.org\/10.1083\/jcb.200701048.","DOI":"10.1083\/jcb.200701048"},{"key":"2025103018011134632_j_jpem-2025-0065_ref_013","doi-asserted-by":"crossref","unstructured":"Fonseca, SG, Burcin, M, Gromada, J, Urano, F. Endoplasmic reticulum stress in beta-cells and development of diabetes. Curr Opin Pharmacol 2009;9:763\u201370. https:\/\/doi.org\/10.1016\/j.coph.2009.07.003.","DOI":"10.1016\/j.coph.2009.07.003"},{"key":"2025103018011134632_j_jpem-2025-0065_ref_014","doi-asserted-by":"crossref","unstructured":"Marr\u00e9, ML, James, EA, Piganelli, JD. \u03b2 cell ER stress and the implications\u00a0for immunogenicity in type 1 diabetes. Front Cell Dev Biol 2015;3:67. https:\/\/doi.org\/10.3389\/fcell.2015.00067.","DOI":"10.3389\/fcell.2015.00067"},{"key":"2025103018011134632_j_jpem-2025-0065_ref_015","unstructured":"Weiss, M, Steiner, DF, Philipson, LH. Insulin biosynthesis, secretion, structure, and structure-activity relationships. In: Feingold, KR, Anawalt, B, Blackman, MR, Boyce, A, Chrousos, G, Corpas, E, et al., editors. Endotext. 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