{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T22:43:29Z","timestamp":1777329809994,"version":"3.51.4"},"reference-count":12,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Microcephaly, Epilepsy, and Diabetes Syndrome 1 (MEDS1) is a very rare autosomal recessive neurodevelopmental disorder (OMIM#614231) characterized by the triad microcephaly with simplified gyration, neonatal permanent diabetes and infantile epileptic encephalopathy. Its occurrence is due to biallelic mutations in the\n                    <jats:italic>IER3IP1<\/jats:italic>\n                    gene, which encodes for the Immediate Early Response 3 Interacting Protein 1 (IER3IP1). To date, only eleven cases have been reported worldwide. Here, we describe the twelfth case from northern Morocco. This 4-month-old patient, born to a healthy non-consanguineous couple presented with microcephaly, epileptic seizures and insulin-requiring permanent neonatal diabetes. Brain MRI revealed simplified gyration with partial agenesis of the corpus callosum. Targeted next generation sequencing identified the patient as compound heterozygous for two\n                    <jats:italic>IER3IP1<\/jats:italic>\n                    variants; a novel nonsense mutation, p. Leu79Ter, and a previously reported pathogenic variant, p. Val21Gly. This report extends the phenotypic and genotypic spectrum of MEDS1 syndrome and provides further evidence of the role of IER3IP1 in neural and pancreatic development, emphasizing the clinical importance of genetic screening in cases of early-onset diabetes and epilepsy especially when accompanied by significant head growth failure in a newborn infant. Further research into the pathophysiology of IER3IP1 may potentially lead to new therapeutic approaches.\n                  <\/jats:p>","DOI":"10.2478\/bjmg-2025-0006","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T04:56:48Z","timestamp":1759985808000},"source":"Crossref","is-referenced-by-count":0,"title":["Microcephaly, Epilepsy, and Diabetes Syndrome 1: A Moroccan Case Report of Novel Compound Heterozygous\n                    <i>IER3IP1<\/i>\n                    Mutations and Literature Review"],"prefix":"10.2478","volume":"28","author":[{"given":"H","family":"Jelti","sequence":"first","affiliation":[{"name":"Department of Medical Genetics and Oncogenetics , Mohammed VI University Hospital center , Tangier , Morocco"},{"name":"Life and Health Sciences Laboratory, Faculty of Medicine and Pharmacy of Tangier , Abdelmalek Assaadi University , Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Khabbache","sequence":"additional","affiliation":[{"name":"Department of pediatrics , Mohammed VI University Hospital center , Tangier , Morocco"},{"name":"Faculty of Medicine and Pharmacy of Tangier , Abdelmalek Assaadi University , Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Bouressas","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Oncogenetics , Mohammed VI University Hospital center , Tangier , Morocco"},{"name":"Life and Health Sciences Laboratory, Faculty of Medicine and Pharmacy of Tangier , Abdelmalek Assaadi University , Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Hacht","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Oncogenetics , Mohammed VI University Hospital center , Tangier , Morocco"},{"name":"Life and Health Sciences Laboratory, Faculty of Medicine and Pharmacy of Tangier , Abdelmalek Assaadi University , Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Oulmaati","sequence":"additional","affiliation":[{"name":"Department of pediatrics , Mohammed VI University Hospital center , Tangier , Morocco"},{"name":"Faculty of Medicine and Pharmacy of Tangier , Abdelmalek Assaadi University , Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Lamzouri","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Oncogenetics , Mohammed VI University Hospital center , Tangier , Morocco"},{"name":"Life and Health Sciences Laboratory, Faculty of Medicine and Pharmacy of Tangier , Abdelmalek Assaadi University , Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"2026042718400984188_j_bjmg-2025-0006_ref_001","doi-asserted-by":"crossref","unstructured":"Poulton CJ, Schot R, Kia SK, Jones M, Verheijen FW, Venselaar H, et al. Microcephaly with Simplified Gyration, Epilepsy, and Infantile Diabetes Linked to Inappropriate Apoptosis of Neural Progenitors. Am J Hum Genet 2011;89:265\u201376. https:\/\/doi.org\/10.1016\/j.ajhg.2011.07.006.","DOI":"10.1016\/j.ajhg.2011.07.006"},{"key":"2026042718400984188_j_bjmg-2025-0006_ref_002","doi-asserted-by":"crossref","unstructured":"Sun J, Ren D. IER3IP1 deficiency leads to increased \u03b2-cell death and decreased \u03b2-cell proliferation. Oncotarget 2017;8:56768\u201379. https:\/\/doi.org\/10.18632\/oncotarget.18179.","DOI":"10.18632\/oncotarget.18179"},{"key":"2026042718400984188_j_bjmg-2025-0006_ref_003","doi-asserted-by":"crossref","unstructured":"Anitei M, Bruno F, Valkova C, Dau T, Cirri E, Mestres I, et al. IER3IP1-mutations cause microcephaly by selective inhibition of ER-Golgi transport. Cell Mol Life Sci 2024;81:334. https:\/\/doi.org\/10.1007\/s00018-024-05386-x.","DOI":"10.1007\/s00018-024-05508-5"},{"key":"2026042718400984188_j_bjmg-2025-0006_ref_004","doi-asserted-by":"crossref","unstructured":"Rjiba K, Soyah N, Kammoun M, Hadj Hmida I, Saad A, Mcelreavey K, et al. Further report of MEDS syndrome: Clinical and molecular delineation of a new Tunisian case. Eur J Med Genet 2021;64:104285. https:\/\/doi.org\/10.1016\/j.ejmg.2021.104285.","DOI":"10.1016\/j.ejmg.2021.104285"},{"key":"2026042718400984188_j_bjmg-2025-0006_ref_005","doi-asserted-by":"crossref","unstructured":"Shalev SA, Tenenbaum-Rakover Y, Horovitz Y, Paz VP, Ye H, Carmody D, et al. Microcephaly, epilepsy, and neonatal diabetes due to compound heterozygous mutations in IER3IP1 : insights into the natural history of a rare disorder: IER3IP1 mutations causing neonatal diabetes and microcephaly. Pediatr Diabetes 2014;15:252\u20136. https:\/\/doi.org\/10.1111\/pedi.12086.","DOI":"10.1111\/pedi.12086"},{"key":"2026042718400984188_j_bjmg-2025-0006_ref_006","doi-asserted-by":"crossref","unstructured":"Abdel-Salam GMH, Schaffer AE, Zaki MS, Dixon-Salazar T, Mostafa IS, Afifi HH, et al. A homozygous IER3IP1 mutation causes microcephaly with simplified gyral pattern, epilepsy, and permanent neonatal diabetes syndrome (MEDS). Am J Med Genet A 2012;158A:2788\u201396. https:\/\/doi.org\/10.1002\/ajmg.a.35583.","DOI":"10.1002\/ajmg.a.35583"},{"key":"2026042718400984188_j_bjmg-2025-0006_ref_007","doi-asserted-by":"crossref","unstructured":"Ellard S, Lango Allen H, De Franco E, Flanagan SE, Hysenaj G, Colclough K, et al. Improved genetic testing for monogenic diabetes using targeted next-generation sequencing. Diabetologia 2013;56:1958\u201363. https:\/\/doi.org\/10.1007\/s00125-013-2962-5.","DOI":"10.1007\/s00125-013-2962-5"},{"key":"2026042718400984188_j_bjmg-2025-0006_ref_008","doi-asserted-by":"crossref","unstructured":"S\u00f6b\u00fc E, Kaya \u00d6z\u00e7ora GD, Y\u0131lmaz G\u00fcle\u00e7 E, \u015eahino\u011flu B, Tahmiscio\u011flu Bucak F. A New Variant of the IER-3IP1 Gene: The First Case of Microcephaly, Epilepsy, and Diabetes Syndrome 1 from Turkey. J Clin Res Pediatr Endocrinol 2022. https:\/\/doi.org\/10.4274\/jcrpe.galenos.2022.2022-8-12.","DOI":"10.4274\/jcrpe.galenos.2022.2022-8-12"},{"key":"2026042718400984188_j_bjmg-2025-0006_ref_009","doi-asserted-by":"crossref","unstructured":"Valenzuela I, Boronat S, Mart\u00ednez-S\u00e1ez E, Clemente M, S\u00e1nchez-Monta\u00f1ez \u00c1, Munell F, et al. Microcephaly with simplified gyral pattern, epilepsy and permanent neonatal diabetes syndrome (MEDS). A new patient and review of the literature. Eur J Med Genet 2017;60:517\u201320. https:\/\/doi.org\/10.1016\/j.ejmg.2017.07.007.","DOI":"10.1016\/j.ejmg.2017.07.007"},{"key":"2026042718400984188_j_bjmg-2025-0006_ref_010","doi-asserted-by":"crossref","unstructured":"Yang J, Zhen J, Feng W, Fan Z, Ding L, Yang X, et al. IER3IP1 is critical for maintaining glucose homeostasis through regulating the endoplasmic reticulum function and survival of \u03b2 cells. Proc Natl Acad Sci 2022;119:e2204443119. https:\/\/doi.org\/10.1073\/pnas.2204443119.","DOI":"10.1073\/pnas.2204443119"},{"key":"2026042718400984188_j_bjmg-2025-0006_ref_011","doi-asserted-by":"crossref","unstructured":"Montaser H, Lepp\u00e4nen S, V\u00e4h\u00e4kangas E, B\u00e4ck N, Grace A, Eurola S, et al. IER3IP1 mutations cause neonatal diabetes due to impaired proinsulin trafficking. Diabetes 2024:db240119. https:\/\/doi.org\/10.2337\/db24-0119.","DOI":"10.2337\/figshare.27245415.v1"},{"key":"2026042718400984188_j_bjmg-2025-0006_ref_012","doi-asserted-by":"crossref","unstructured":"Zegarra WA, Gallentine WB, Ruzhnikov MR, McAndrews CA, Gloyn AL, Addala A. Safe use of the ketogenic diet in an infant with microcephaly, epilepsy, and diabetes syndrome: a case report. BMC Pediatr 2023;23:453. https:\/\/doi.org\/10.1186\/s12887-023-04272-y.","DOI":"10.1186\/s12887-023-04272-y"}],"container-title":["Balkan Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/reference-global.com\/pdf\/10.2478\/bjmg-2025-0006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T22:09:48Z","timestamp":1777327788000},"score":1,"resource":{"primary":{"URL":"https:\/\/reference-global.com\/article\/10.2478\/bjmg-2025-0006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,1]]},"references-count":12,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,10,8]]},"published-print":{"date-parts":[[2025,6,1]]}},"alternative-id":["10.2478\/bjmg-2025-0006"],"URL":"https:\/\/doi.org\/10.2478\/bjmg-2025-0006","relation":{},"ISSN":["2199-5761"],"issn-type":[{"value":"2199-5761","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,1]]},"article-number":"20250006"}}