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Microcephaly, Epilepsy, and Diabetes Syndrome 1: A Moroccan Case Report of Novel Compound Heterozygous IER3IP1 Mutations and Literature Review

Open Access
|Oct 2025

References

  1. 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;89:265–76. https://doi.org/10.1016/j.ajhg.2011.07.006.
  2. Sun J, Ren D. IER3IP1 deficiency leads to increased β-cell death and decreased β-cell proliferation. Oncotarget 2017;8:56768–79. https://doi.org/10.18632/oncotarget.18179.
  3. 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.
  4. 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.
  5. 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;15:252–6. https://doi.org/10.1111/pedi.12086.
  6. 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:2788–96. https://doi.org/10.1002/ajmg.a.35583.
  7. 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;56:1958–63. https://doi.org/10.1007/s00125-013-2962-5.
  8. Söbü E, Kaya Özçora GD, Yılmaz Güleç E, Şahinoğlu B, Tahmiscioğlu 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.
  9. Valenzuela I, Boronat S, Martínez-Sáez E, Clemente M, Sánchez-Montañez Á, 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;60:517–20. https://doi.org/10.1016/j.ejmg.2017.07.007.
  10. 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 β cells. Proc Natl Acad Sci 2022;119:e2204443119. https://doi.org/10.1073/pnas.2204443119.
  11. Montaser H, Leppänen S, Vähäkangas E, Bäck 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.
  12. 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.
Language: English
Published on: Oct 8, 2025
Published by: Macedonian Academy of Sciences and Arts
In partnership with: Paradigm Publishing Services
Publication frequency: 2 times per year

© 2025 H Jelti, K Khabbache, S Bouressas, F Hacht, A Oulmaati, A Lamzouri, published by Macedonian Academy of Sciences and Arts
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.