Generic placeholder image

Current Diabetes Reviews

Editor-in-Chief

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

Mini-Review Article

Maturity-onset Diabetes of the Young Type 7 (MODY7) and the Krüppellike Factor 11 Mutation (KLF11). A Review

Author(s): Pedro Mancera-Rincón, Maria Camila Luna-España, Oswaldo Rincon, Issac Guzmán and Mauricio Alvarez*

Volume 20, Issue 1, 2024

Published on: 11 April, 2023

Article ID: e210323214817 Pages: 5

DOI: 10.2174/1573399819666230321114456

Price: $65

Abstract

Introduction: Maturity-onset diabetes of the young (MODY) is a rare disease due to a single gene mutation that affects several family members in most cases. The Krüppel-like factor 11 (KLF11) gene mutation is associated with decreased insulin sensitivity to high glucose levels. KLF 11 has been implicated in the pathogenesis of MODY type 7 but given its low prevalence, prolonged subclinical period, and the emergence of new information, doubts are raised about its association.

Methods: A literature search of the PubMed, Scopus, and EBSCO databases was performed. The terms “Diabetes Mellitus, Type 2/genetics”, “Mason-Type Diabetes” , “Maturity-Onset diabetes of the young”, “KLF11 protein, human”, and “Maturity-Onset Diabetes of the Young, Type 7” were used”., “Diagnosis” The search selection was not standardized.

Results: The KLF1 mutation is rare and represents <1% of the mutations associated with monogenic diabetes. Its isolation in European family lines in the first studies and the emergence of new variants pose new diagnostic challenges. This article reviews the definition, epidemiology, pathophysiology, diagnosis, and treatment of MODY type 7.

Conclusion: MODY type 7 diabetes represents a rare form of monogenic diabetes with incomplete penetrance. Given its rarity, its association with impaired glucose metabolism has been questioned. Strict evaluation of glycemic control and the appearance of microvascular complications are key areas in the follow-up of patients diagnosed with MODY 7. More studies will be required to characterize the population with KLF11 mutation and clarify its correlation with MODY.

Keywords: KLF11, MODY7, maturity-onset diabetes of the young, diabetes mellitus, monogenic diabetes, epidemiology.

[1]
Fajans SS, Conn JW. Tolbutamide-induced improvement in carbohydrate tolerance of young people with mild diabetes mellitus. Diabetes 1960; 9(2): 83-8.
[http://dx.doi.org/10.2337/diab.9.2.83] [PMID: 13821363]
[2]
Tattersall RB. Mild familial diabetes with dominant inheritance. Q J Med 1974; 43(170): 339-57.
[PMID: 4212169]
[3]
Vionnet N, Stoffel M, Takeda J, et al. Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus. Nature 1992; 356(6371): 721-2.
[http://dx.doi.org/10.1038/356721a0] [PMID: 1570017]
[4]
Yamagata K, Furuta H, Oda N, et al. Mutations in the hepatocyte nuclear factor-4α gene in maturity-onset diabetes of the young (MODY1). Nature 1996; 384(6608): 458-60.
[http://dx.doi.org/10.1038/384458a0] [PMID: 8945471]
[5]
Yamagata K, Oda N, Kaisaki PJ, et al. Mutations in the hepatocyte nuclear factor-1α gene in maturity-onset diabetes of the young (MODY3). Nature 1996; 384(6608): 455-8.
[http://dx.doi.org/10.1038/384455a0] [PMID: 8945470]
[6]
Broome DT, Pantalone KM, Kashyap SR, Philipson LH. Approach to the patient with MODY-monogenic diabetes. J Clin Endocrinol Metab 2021; 106(1): 237-50.
[http://dx.doi.org/10.1210/clinem/dgaa710] [PMID: 33034350]
[7]
Neve B, Fernandez-Zapico ME, Ashkenazi-Katalan V, et al. Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic beta cell function. Proc Natl Acad Sci 2005; 102(13): 4807-12.
[http://dx.doi.org/10.1073/pnas.0409177102] [PMID: 15774581]
[8]
Shepherd M, Shields B, Hammersley S, et al. Systematic population screening, using biomarkers and genetic testing, identifies 2.5% of the U.K. pediatricdiabetes population with monogenic diabetes. Diabetes Care 2016; 39(11): 1879-88.
[http://dx.doi.org/10.2337/dc16-0645] [PMID: 27271189]
[9]
Pihoker C, Gilliam LK, Ellard S, et al. Prevalence, characteristics and clinical diagnosis of maturity onset diabetes of the young due to mutations in HNF1A, HNF4A, and glucokinase: Results from the SEARCH for Diabetes in Youth. J Clin Endocrinol Metab 2013; 98(10): 4055-62.
[http://dx.doi.org/10.1210/jc.2013-1279] [PMID: 23771925]
[10]
Ma L, Hanson RL, Que LN, et al. Association analysis of Krüppel-like factor 11 variants with type 2 diabetes in Pima Indians. J Clin Endocrinol Metab 2008; 93(9): 3644-9.
[http://dx.doi.org/10.1210/jc.2008-0546] [PMID: 18593768]
[11]
Tanahashi T, Shinohara K, Keshavarz P, et al. The association of genetic variants in Krüppel-like factor 11 and Type 2 diabetes in the Japanese population. Diabet Med 2008; 25(1): 19-26.
[http://dx.doi.org/10.1111/j.1464-5491.2007.02315.x] [PMID: 18199129]
[12]
Cook T, Gebelein B, Mesa K, Mladek A, Urrutia R. Molecular cloning and characterization of TIEG2 reveals a new subfamily of transforming growth factor-β-inducible Sp1-like zinc finger-encoding genes involved in the regulation of cell growth. J Biol Chem 1998; 273(40): 25929-36.
[http://dx.doi.org/10.1074/jbc.273.40.25929] [PMID: 9748269]
[13]
Scohy S, Gabant P, Van Reeth T, et al. Identification of KLF13 and KLF14 (SP6), novel members of the SP/XKLF transcription factor family. Genomics 2000; 70(1): 93-101.
[http://dx.doi.org/10.1006/geno.2000.6362] [PMID: 11087666]
[14]
Sun Y, Qu J, Wang J, Zhao R, Wang C, Chen L, et al. Clinical and functional characteristics of a novel KLF11 Cys354Phe variant involved in maturity-onset diabetes of the young. Kong X, editor J. J Diabetes Res 2021; Feb 1 2021: pp. 1-10.
[http://dx.doi.org/10.1155/2021/7136869] [PMID: 33604390]
[15]
Ushijima K, Narumi S, Ogata T, Yokota I, Sugihara S, Kaname T. KLF11 variant in a family clinically diagnosed with early childhood‐onset type 1B diabetes. Pediatr Diabetes 2019; 20(6): pedi.12868.
[http://dx.doi.org/10.1111/pedi.12868]
[16]
Fernandez-Zapico ME, Mladek A, Ellenrieder V, Folch-Puy E, Miller L, Urrutia R. An mSin3A interaction domain links the transcriptional activity of KLF11 with its role in growth regulation. EMBO J 2003; 22(18): 4748-58.
[http://dx.doi.org/10.1093/emboj/cdg470] [PMID: 12970187]
[17]
Robertson RP, Harmon J, Tran POT, Poitout V. β-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes Diabetes 2004; 53(S1): S119-24.
[http://dx.doi.org/10.2337/diabetes.53.2007.S119] [PMID: 14749276]
[18]
McDonald TJ, Colclough K, Brown R, et al. Islet autoantibodies can discriminate maturity-onset diabetes of the young (MODY) from Type 1 diabetes. Diabet Med 2011; 28(9): 1028-33.
[http://dx.doi.org/10.1111/j.1464-5491.2011.03287.x] [PMID: 21395678]
[19]
Ellard S, Bellanné-Chantelot C, Hattersley AT. Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young. Diabetologia 2008; 51(4): 546-53.
[http://dx.doi.org/10.1007/s00125-008-0942-y] [PMID: 18297260]
[20]
Urakami T. Maturity-onset diabetes of the young (MODY): Current perspectives on diagnosis and treatment. Diabetes Metab Syndr Obes 2019; 12: 1047-56.
[http://dx.doi.org/10.2147/DMSO.S179793] [PMID: 31360071]
[21]
Alvarez M, Rincon O, Alvarado A, Puentes F. Maturity-onset diabetes of the young type 3 and premature ovarian insufficiency: chance or causality: a case report and literature review. Endocrinol Diabetes Metab Case Rep 2022; 2022: 21-0166.
[http://dx.doi.org/10.1530/EDM-21-0166] [PMID: 35615950]
[22]
Nkonge KM, Nkonge DK, Nkonge TN. The epidemiology, molecular pathogenesis, diagnosis, and treatment of maturity-onset diabetes of the young (MODY). Clin Diabetes Endocrinol 2020; 6(1): 20.
[http://dx.doi.org/10.1186/s40842-020-00112-5] [PMID: 33292863]
[23]
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(S27): 47-63.
[http://dx.doi.org/10.1111/pedi.12772] [PMID: 30225972]
[24]
Jones AG, Hattersley AT. The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet Med 2013; 30(7): 803-17.
[http://dx.doi.org/10.1111/dme.12159] [PMID: 23413806]
[25]
Oliveira SC, Neves JS, Pérez A, Carvalho D. Maturity-onset diabetes of the young: From a molecular basis perspective toward the clinical phenotype and proper management. Endocrinología Diabetesy Nutrrición 2020; 67(2): 137-47.
[http://dx.doi.org/10.1016/j.endien.2020.03.001] [PMID: 31718996]
[26]
Aarthy R, Aston-Mourney K, Mikocka-Walus A, et al. Clinical features, complications and treatment of rarer forms of maturity-onset diabetes of the young (MODY) - A review. J Diabetes Complications 2021; 35(1): 107640.
[http://dx.doi.org/10.1016/j.jdiacomp.2020.107640] [PMID: 32763092]
[27]
Shields BM, McDonald TJ, Ellard S, Campbell MJ, Hyde C, Hattersley AT. The development and validation of a clinical prediction model to determine the probability of MODY in patients with young-onset diabetes. Diabetologia 2012; 55(5): 1265-72.
[http://dx.doi.org/10.1007/s00125-011-2418-8] [PMID: 22218698]
[28]
Besser REJ, Shepherd MH, McDonald TJ, et al. Urinary C-peptide creatinine ratio is a practical outpatient tool for identifying hepatocyte nuclear factor 1-α/hepatocyte nuclear factor 4-α maturity-onset diabetes of the young from long-duration type 1 diabetes. Diabetes Care 2011; 34(2): 286-91.
[http://dx.doi.org/10.2337/dc10-1293] [PMID: 21270186]
[29]
Naylor RN, John PM, Winn AN, et al. Cost-effectiveness of MODY genetic testing: Translating genomic advances into practical health applications. Diabetes Care 2014; 37(1): 202-9.
[http://dx.doi.org/10.2337/dc13-0410] [PMID: 24026547]
[30]
Johansson S, Irgens H, Chudasama KK, Molnes J, Aerts J, Roque FS. Exome sequencing and genetic testing for MODY. Plos One 2012; 7(5): e38050.
[http://dx.doi.org/10.1371/journal.pone.0038050]
[31]
Laver TW, Wakeling MN, Knox O, et al. Evaluation of evidence for pathogenicity demonstrates that BLK, KLF11, and PAX4 should not be included in diagnostic testing for MODY. Diabetes 2022; 71(5): 1128-36.
[http://dx.doi.org/10.2337/db21-0844] [PMID: 35108381]
[32]
Misra S, Owen KR. Genetics of monogenic diabetes: Present clinical challenges. Curr Diab Rep 2018; 18(12): 141.
[http://dx.doi.org/10.1007/s11892-018-1111-4] [PMID: 30377832]
[33]
Fajans SS, Brown MB. Administration of sulfonylureas can increase glucose-induced insulin secretion for decades in patients with maturity-onset diabetes of the young. Diabetes Care 1993; 16(9): 1254-61.
[http://dx.doi.org/10.2337/diacare.16.9.1254] [PMID: 8404429]
[34]
Fajans SS, Bell GI. MODY: History, genetics, pathophysiology, and clinical decision making. Diabetes Care 2011; 34(8): 1878-84.
[http://dx.doi.org/10.2337/dc11-0035] [PMID: 21788644]
[35]
Kleinberger JW, Copeland KC, Gandica RG, et al. Monogenic diabetes in overweight and obese youth diagnosed with type 2 diabetes: The TODAY clinical trial. Genet Med 2018; 20(6): 583-90.
[http://dx.doi.org/10.1038/gim.2017.150] [PMID: 29758564]
[36]
Mohan V, Radha V, Nguyen TT, et al. Comprehensive genomic analysis identifies pathogenic variants in maturity-onset diabetes of the young (MODY) patients in South India. BMC Med Genet 2018; 19(1): 22.
[http://dx.doi.org/10.1186/s12881-018-0528-6] [PMID: 29439679]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy