MODY caused by a mutation in the insulin gene
https://doi.org/10.14341/DM12807
Abstract
MODY10 is a rare subtype of MODY diabetes, which caused by heterozygous mutations in the insulin gene INS. There are single descriptions of families with MODY-INS or MODY10 in the literature, its clinical course is not well understood. We present a case of MODY10 in a boy with a history of diabetes mellitus (DM) in three generations (father and paternal grandmother). Proband was diagnosed with diabetes mellitus at the age of 7 years. The glycaemia at the onset of the diabetes was 10.2 mmol/l, HbA1c — 7.6%, islet cell autoantibodies (ICA), insulin autoantibodies (IAA), glutamic acid decarboxylase antibodies (GADA) and islet tyrosine phosphatase 2 (IA2) antibodies (IA2) were not detected. According to the results of the oral glucose tolerance test, fasting blood glucose was 6.5 mmol/l, in 120 minutes 10.3 mmol/l, which corresponded to the diagnosis of impaired glucose tolerance. Diet with restriction of easily digestible carbohydrates was recommended, than gliclazide was added to the therapy, which the proband received for 3 years. At the age of 10, a deterioration in the parameters of carbohydrate metabolism was noted, which insulin therapy was added. Examination at the age of 12 revealed a decrease in C-peptide secretion. The child’s father has a similar phenotype — slowly progressive disorders of carbohydrate metabolism from 6 years old, from 10 years old — insulin therapy. A genetic test was provided, in the child and his father was detected a previously undescribed heterozygous mutation in the INS p.C31W. Thus, in our clinical case, MODY10 was characterized by a milder course than T1DM, but eventually leading to the development of insulin demand, which distinguishes it from the most common forms of MODY. Currently, there is no specific therapy, and the detection of a mutation in the INS gene does not affect therapeutic tactics, however, a correct genetic diagnosis makes it possible to predict the course of diabetes and provide genetic counseling to the family.
About the Authors
E. A. SechkoRussian Federation
Elena A. Sechko - MD, PhD; eLibrary SPIN: 4608-5650
11 Dm. Ulyanova street, Moscow 117292
Competing Interests:
none
T. L. Kuraeva
Russian Federation
Tamara L. Kuraeva - MD, PhD, Professor; eLibrary SPIN: 8206-0406/
Moscow
Competing Interests:
none
E. A. Andrianova
Russian Federation
Ekaterina A. Andrianova - MD, PhD; eLibrary SPIN: 7496-4580
Moscow
Competing Interests:
none
L. I. Zilberman
Russian Federation
Lubov I. Zilberman - MD, PhD; eLibrary SPIN 4488-7724.
Moscow
Competing Interests:
none
A. O. Emelyanov
Russian Federation
Andrey O. Emelyanov - PhD; eLibrary SPIN: 8110-5540.
Moscow
Competing Interests:
none
D. N. Laptev
Russian Federation
Dmitry N. Laptev - PhD; eLibrary SPIN: 2419-4019.
Moscow
Competing Interests:
none
O. B. Bezlepkina
Russian Federation
Olga B. Bezlepkina - MD, PhD, Professor; eLibrary SPIN: 3884-0945.
Moscow
Competing Interests:
none
References
1. 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. doi: https://doi.org/10.1111/pedi.12772
2. Thanabalasingham G, Owen KR. Diagnosis and management of maturity onset diabetes of the young (MODY). BMJ. 2011;343(3):d6044-d6044. doi: https://doi.org/10.1136/bmj.d6044
3. Shields BM, Hicks S, Shepherd MH, et al. Maturity-onset diabetes of the young (MODY): how many cases are we missing? Diabetologia. 2010;53(12):2504-2508. doi: https://doi.org/10.1007/s00125-010-1799-4
4. Kavvoura FK, Owen KR. Maturity onset diabetes of the young: clinical characteristics, diagnosis and management. Pediatr Endocrinol Rev. 2012;10(2):234-242.
5. Belovalova IM, Kandror VI. Osnovy regulyacii obmena veshestv v norme i pri sakharnom diabete. In: Sakharnyi diabet: daignistika, lechenie, profilaktika. Ed. by Dedova II, Shestakovoi MV. Moscow: MIA; 2011. P. 41-93. (In Russ.).
6. Meur G, Simon A, Harun N, et al. Insulin gene mutations resulting in early-onset diabetes: marked differences in clinical presentation, metabolic status, and pathogenic effect through endoplasmic reticulum retention. Diabetes. 2010;59(3):653-661. doi: https://doi.org/10.2337/db09-1091
7. Støy J, Edghill EL, Flanagan SE, et al. Insulin gene mutations as a cause of permanent neonatal diabetes. Proc Natl Acad Sci U S A. 2007;104(38):15040-15044. doi: https://doi.org/10.1073/pnas.0707291104
8. Slingerland AS, Shields BM, Flanagan SE, et al. Referral rates for diagnostic testing support an incidence of permanent neonatal diabetes in three European countries of at least 1 in 260,000 live births. Diabetologia. 2009;52(8):1683-1685. doi: https://doi.org/10.1007/s00125-009-1416-6
9. Edghill EL, Flanagan SE, Patch AM, et al. Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood. Diabetes. 2008;57(4):1034-1042. doi: https://doi.org/10.2337/db07-1405
10. Bonfanti R, Colombo C, Nocerino V, et al. Insulin gene mutations as cause of diabetes in children negative for five type 1 diabetes autoantibodies. Diabetes Care. 2009;32(1):123-125. doi: https://doi.org/10.2337/dc08-0783
11. Molven A, Ringdal M, Nordbø AM, et al. Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes. Diabetes. 2008;57(4):1131-1135. doi: https://doi.org/10.2337/db07-1467
12. Rajan S, Eames SC, Park SY, et al. In vitro processing and secretion of mutant insulin proteins that cause permanent neonatal diabetes. Am J Physiol Endocrinol Metab. 2010;298(3):E403-E410. doi: https://doi.org/10.1152/ajpendo.00592.2009
13. 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):583-590. doi: https://doi.org/10.1038/gim.2017.150
14. 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. doi: https://doi.org/10.1016/j.jdiacomp.2020.107640
15. Boesgaard TW, Pruhova S, Andersson EA, et al. Further evidence that mutations in INS can be a rare cause of Maturity-Onset Diabetes of the Young (MODY). BMC Med Genet. 2010;11:42. doi: https://doi.org/10.1186/1471-2350-11-42
16. Kuraeva TL, Sechko EA, Zilberman LI, et al. Molecular genetic and clinical variants MODY2 and MODY3 in children in Russia. Problems of Endocrinology. 2015;61(5):14-25. (In Russ.). doi: https://doi.org/10.14341/probl201561514-25
17. Zubkova NA, Gioeva OA, Tikhonovich YuV, et al. Clinical and molecular genetic characteristics of MODY1–3 cases in the Russian Federation as shown by NGS. Problems of Endocrinology. 2017;63(6):369-378. (In Russ.). doi: https://doi.org/10.14341/probl2017636369-378
18. Liu M, Sun J, Cui J, et al. INS-gene mutations: from genetics and beta cell biology to clinical disease. Mol Aspects Med. 2015;42:3-18. doi: https://doi.org/10.1016/j.mam.2014.12.001
19. Dusatkova L, Dusatkova P, Vosahlo J, et al. Frameshift mutations in the insulin gene leading to prolonged molecule of insulin in two families with Maturity-Onset Diabetes of the Young. Eur J Med Genet. 2015;58(4):230-234. doi: https://doi.org/10.1016/j.ejmg.2015.02.004
20. Xiao X, Liu L, Xiao Y, et al. Novel frameshift mutation in the insulin (INS) gene in a family with maturity onset diabetes of the young (MODY). J Diabetes. 2019;11(1):83-86. doi: https://doi.org/10.1111/1753-0407.12849
Supplementary files
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1. Рисунок 1. Родословная семьи. НТГ – нарушенная толерантность к глюкозе | |
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Type | Материалы исследования | |
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For citations:
Sechko E.A., Kuraeva T.L., Andrianova E.A., Zilberman L.I., Emelyanov A.O., Laptev D.N., Bezlepkina O.B. MODY caused by a mutation in the insulin gene. Diabetes mellitus. 2022;25(1):89-94. (In Russ.) https://doi.org/10.14341/DM12807

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