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Current Diabetes Reviews

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ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

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Systematic Review Article

What Do We Know about Neonatal Diabetes Caused by PDX1 Mutations?

In Press, (this is not the final "Version of Record"). Available online 29 January, 2024
Author(s): Ritiele Bastos de Souza, Pedro Hernán Cabello, Eliane Lopes Rosado, Mário Campos Junior and Gabriella de Medeiros Abreu*
Published on: 29 January, 2024

Article ID: e290124226471

DOI: 10.2174/0115733998265866231204070606

Price: $95

Abstract

Introduction: Neonatal diabetes mellitus (NDM) is characterized by severe hyperglycemia, usually diagnosed in the first few months of an individual’s life. It is a genetic disease and one of the main forms of monogenic diabetes. Changes in different genes have already been associated with NDM, including changes in the gene PDX1.

Methods: In this review, we intend to summarize all neonatal diabetes cases caused by PDX1 mutations reported in the literature. For this purpose, we searched keywords in the literature from PubMed and articles cited by the HGMD database. The search retrieved 84 articles, of which 41 had their full text accessed. After applying the study exclusion criteria, nine articles were included.

Results: Of those articles, we detected thirteen cases of NDM associated with changes in PDX1; the majority in homozygous or compound heterozygous patients. Until now, variants in the PDX1 gene have been a rare cause of NDM; however, few studies have included the screening of this gene in the investigation of neonatal diabetes.

Conclusion: In this review, we reinforce the importance of the PDX1 gene inclusion in genetic NGS panels for molecular diagnosis of NDM, and systematic morphological and functional exams of the pancreas when NDM is present.

[1]
Care D, Suppl SS. 2. Classification and diagnosis of diabetes: Standards of medical care in diabetes-2021. Diabetes Care 2021; 44 (Suppl. 1): S15-33.
[http://dx.doi.org/10.2337/dc21-S002] [PMID: 33298413]
[2]
De Franco E, Flanagan SE, Houghton JAL, et al. The effect of early, comprehensive genomic testing on clinical care in neonatal diabetes: An international cohort study. Lancet 2015; 386(9997): 957-63.
[http://dx.doi.org/10.1016/S0140-6736(15)60098-8] [PMID: 26231457]
[3]
Greeley SAW, Tucker SE, Naylor RN, Bell GI, Philipson LH. Neonatal diabetes mellitus: A model for personalized medicine. Trends Endocrinol Metab 2010; 21(8): 464-72.
[http://dx.doi.org/10.1016/j.tem.2010.03.004] [PMID: 20434356]
[4]
Yang Y, Chan L. Monogenic Diabetes: What It Teaches Us on the Common Forms of Type 1 and Type 2 Diabetes. Endocr Rev 2016; 37(3): 190-222.
[http://dx.doi.org/10.1210/er.2015-1116] [PMID: 27035557]
[5]
Hattersley AT, Greeley SAW, Polak M, et al. ISPAD Clinical Practice Consensus Guidelines 2018: The diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes 2018; 19 (Suppl. 27): 47-63.
[http://dx.doi.org/10.1111/pedi.12772] [PMID: 30225972]
[6]
Grulich-Henn J, Wagner V, Thon A, et al. Entities and frequency of neonatal diabetes: Data from the diabetes documentation and quality management system (DPV). Diabet Med 2010; 27(6): 709-12.
[http://dx.doi.org/10.1111/j.1464-5491.2010.02965.x] [PMID: 20546293]
[7]
Dahl A, Kumar S. Recent advances in neonatal diabetes. Diabetes. Diabetes Metab Syndr Obes 2020; 13: 355-64.
[http://dx.doi.org/10.2147/DMSO.S198932] [PMID: 32104032]
[8]
Nayak S, Sarangi AN, Sahoo SK, et al. Neonatal Diabetes Mellitus: Novel Mutations. Indian J Pediatr 2021; 88(8): 785-92.
[http://dx.doi.org/10.1007/s12098-020-03567-7] [PMID: 33409956]
[9]
Naylor RN, Greeley SAW, Bell GI, Philipson LH. Genetics and pathophysiology of neonatal diabetes mellitus. J Diabetes Investig 2011; 2(3): 158-69.
[http://dx.doi.org/10.1111/j.2040-1124.2011.00106.x] [PMID: 24843477]
[10]
Beltrand J, Busiah K, Vaivre-Douret L, et al. Neonatal Diabetes Mellitus. Front Pediatr 2020; 8: 540718.
[http://dx.doi.org/10.3389/fped.2020.540718] [PMID: 33102403]
[11]
Aguilar-Bryan L, Bryan J. Neonatal diabetes mellitus. Endocr Rev 2008; 29(3): 265-91.
[http://dx.doi.org/10.1210/er.2007-0029] [PMID: 18436707]
[12]
Temple IK, Shield JPH. 6q24 transient neonatal diabetes. Rev Endocr Metab Disord 2010; 11(3): 199-204.
[http://dx.doi.org/10.1007/s11154-010-9150-4] [PMID: 20922569]
[13]
Schwitzgebel VM, Mamin A, Brun T, et al. Agenesis of human pancreas due to decreased half-life of insulin promoter factor 1. J Clin Endocrinol Metab 2003; 88(9): 4398-406.
[http://dx.doi.org/10.1210/jc.2003-030046] [PMID: 12970316]
[14]
Wang X, Sterr M, Ansarullah , et al. Point mutations in the PDX1 transactivation domain impair human β-cell development and function. Mol Metab 2019; 24: 80-97.
[http://dx.doi.org/10.1016/j.molmet.2019.03.006] [PMID: 30930126]
[15]
Ohlsson H, Karlsson K, Edlund T. IPF1, a homeodomain-containing transactivator of the insulin gene. EMBO J 1993; 12(11): 4251-9.
[http://dx.doi.org/10.1002/j.1460-2075.1993.tb06109.x] [PMID: 7901001]
[16]
Watada H, Kajimoto Y, Umayahara Y, et al. The human glucokinase gene β-cell-type promoter: An essential role of insulin promoter factor 1/PDX-1 in its activation in HIT-T15 cells. Diabetes 1996; 45(11): 1478-88.
[http://dx.doi.org/10.2337/diab.45.11.1478] [PMID: 8866550]
[17]
Watada H, Kajimoto Y, Kaneto H, et al. Involvement of the homeodomain-containing transcription factor PDX-1 in islet amyloid polypeptide gene transcription. Biochem Biophys Res Commun 1996; 229(3): 746-51.
[http://dx.doi.org/10.1006/bbrc.1996.1875] [PMID: 8954967]
[18]
Waeber G, Thompson N, Nicod P, Bonny C. Transcriptional activation of the GLUT2 gene by the IPF-1/STF-1/IDX-1 homeobox factor. Mol Endocrinol 1996; 10(11): 1327-34.
[http://dx.doi.org/10.1210/mend.10.11.8923459] [PMID: 8923459]
[19]
Marshak S, Benshushan E, Shoshkes M, Havin L, Cerasi E, Melloul D. Functional conservation of regulatory elements in the pdx-1 gene: PDX-1 and hepatocyte nuclear factor 3β transcription factors mediate β-cell-specific expression. Mol Cell Biol 2000; 20(20): 7583-90.
[http://dx.doi.org/10.1128/MCB.20.20.7583-7590.2000] [PMID: 11003654]
[20]
Babu DA, Deering TG, Mirmira RG. A feat of metabolic proportions: Pdx1 orchestrates islet development and function in the maintenance of glucose homeostasis. Mol Genet Metab 2007; 92(1-2): 43-55.
[http://dx.doi.org/10.1016/j.ymgme.2007.06.008] [PMID: 17659992]
[21]
Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17(5): 405-24.
[http://dx.doi.org/10.1038/gim.2015.30] [PMID: 25741868]
[22]
Kopanos C, Tsiolkas V, Kouris A, et al. VarSome: The human genomic variant search engine. Bioinformatics 2019; 35(11): 1978-80.
[http://dx.doi.org/10.1093/bioinformatics/bty897] [PMID: 30376034]
[23]
De Franco E, Shaw-Smith C, Flanagan SE, et al. Biallelic PDX1 (insulin promoter factor 1) mutations causing neonatal diabetes without exocrine pancreatic insufficiency. Diabet Med 2013; 30(5): e197-200.
[http://dx.doi.org/10.1111/dme.12122] [PMID: 23320570]
[24]
Ellard S, Lango Allen H, De Franco E, et al. Improved genetic testing for monogenic diabetes using targeted next-generation sequencing. Diabetologia 2013; 56(9): 1958-63.
[http://dx.doi.org/10.1007/s00125-013-2962-5] [PMID: 23771172]
[25]
Stoffers DA, Zinkin NT, Stanojevic V, Clarke WL, Habener JF. Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence. Nat Genet 1997; 15(1): 106-10.
[http://dx.doi.org/10.1038/ng0197-106] [PMID: 8988180]
[26]
Staffers DA, Ferrer J, Clarke WL, Habener JF. Early-onset type-ll diabetes mellitus (MODY4) linked to IPF1. Nat Genet 1997; 17(2): 138-9.
[http://dx.doi.org/10.1038/ng1097-138] [PMID: 9326926]
[27]
Clocquet AR, Egan JM, Stoffers DA, et al. Impaired insulin secretion and increased insulin sensitivity in familial maturity-onset diabetes of the young 4 (insulin promoter factor 1 gene). Diabetes 2000; 49(11): 1856-64.
[http://dx.doi.org/10.2337/diabetes.49.11.1856] [PMID: 11078452]
[28]
Thomas IH, Saini NK, Adhikari A, et al. Neonatal diabetes mellitus with pancreatic agenesis in an infant with homozygous IPF-1 Pro63fsX60 mutation. Pediatr Diabetes 2009; 10(7): 492-6.
[http://dx.doi.org/10.1111/j.1399-5448.2009.00526.x] [PMID: 19496967]
[29]
Fajans SS, Bell GI, Paz VP, et al. Obesity and hyperinsulinemia in a family with pancreatic agenesis and MODY caused by the IPF1 mutation Pro63fsX60. Transl Res 2010; 156(1): 7-14.
[http://dx.doi.org/10.1016/j.trsl.2010.03.003] [PMID: 20621032]
[30]
Kulkarni A, Sharma VK, Nabi F. PDX1 gene mutation with permanent neonatal diabetes mellitus with annular pancreas, duodenal atresia, hypoplastic gall bladder and exocrine pancreatic insufficiency. Indian Pediatr 2017; 54(12): 1052-3.
[http://dx.doi.org/10.1007/s13312-017-1211-2] [PMID: 29317564]
[31]
Sahebi L, Niknafs N, Dalili H, et al. Iranian neonatal diabetes mellitus due to mutation in PDX1 gene: A case report. J Med Case Reports 2019; 13(1): 258.
[http://dx.doi.org/10.1186/s13256-019-2149-x] [PMID: 31366392]
[32]
Nicolino M, Claiborn KC, Senée V, Boland A, Stoffers DA, Julier C. A novel hypomorphic PDX1 mutation responsible for permanent neonatal diabetes with subclinical exocrine deficiency. Diabetes 2010; 59(3): 733-40.
[http://dx.doi.org/10.2337/db09-1284] [PMID: 20009086]
[33]
Korula S, Ravichandran L, Paul P, et al. Genetic heterogeneity and challenges in the management of permanent neonatal diabetes mellitus: A single-centre study from South India. Indian J Endocrinol Metab 2022; 26(1): 79-86.
[http://dx.doi.org/10.4103/ijem.ijem_429_21] [PMID: 35662751]
[34]
Abreu GM, Tarantino RM, da Fonseca ACP, et al. PDX1-MODY: A rare missense mutation as a cause of monogenic diabetes. Eur J Med Genet 2021; 64(5): 104194.
[http://dx.doi.org/10.1016/j.ejmg.2021.104194] [PMID: 33746035]
[35]
World Health Organization. Low birth weight data from the Nutrition Landscape Information System (NLIS). 2023. Available From: https://www.who.int/data/nutrition/nlis/info/low-birth

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