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Published: 2021-05-31
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DOI: https://doi.org/10.52852/tcncyh.v138i2.71
Issue
Vol. 138 No. 2 (2021)
Section
Các bài báo
How to Cite
Ngọc, C. T. B., & Dũng, V. C. (2021). Dominant heterozygous c.991t>c of the kcnj11 gene causes various phenotype of diabetes mellitus . Journal of Medical Research, 138(2), 49-54. https://doi.org/10.52852/tcncyh.v138i2.71

Dominant heterozygous c.991t>c of the kcnj11 gene causes various phenotype of diabetes mellitus

Cấn Thị Bích Ngọc, Vũ Chí Dũng

Main Article Content

Abstract

Activating mutations of the KCNJ11 gene, which encodes Kir6.2 (beta-cell adenosine triphosphate-sensitive potassium [KATP] channel subunit), have been associated with neonatal diabetes mellitus (NDM). Treatment with oral Sulfonylurea (SU) in place of exogenous insulin injections results in improved glycemic control in most patients carrying these mutations. Exploration of genetic causes of NDM occurring before 6 months of age has been proposed as an important issue in the identification of monogenic forms of diabetes, which might be critical in their therapeutic management. Three members with diabetes in one family were described: the proband (II.2), diagnosed at 62 days of age; his sibling (II.3), diagnosed at 13 months of age, and their father (I.2), diagnosed at 20 years of age. Analysis of coding and flanking intronic regions of the KCNJ11, INS and ABCC8 genes by Sanger sequencing was performed.


Three patients has heterozygous for the novel KCNJ11 missense variant, p.(Ser331Pro). Patient II.2 and II.3 had been transferred to SU from insulin with improved glycemic control. Patient I.2 has been treated with insulin due to refusal to switch to SU. This mutation in KCNJ11 cause diabetes mellitus in neonatal, childhood or adulthood.

Article Details

Keywords

diabetes mellitus, KCNJ11, Kir6.2, neonatal diabetes

References

1. Gloyn AL, Pearson ER, Antcliff JF et al. Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N Engl J Med. 2004;350(18):1838– 1849.
2. Inagaki N, Gonoi T, and Seino S. Subunit stoichiometry of the pancreatic beta-cell ATP-sensitive K+ channel. FEBS Lett.1997;409(2): 232– 236.
3. Tusnády GE, Bakos É, Váradi A et al. Membrane topology distinguishes a subfamily of the ATP-binding cassette (ABC) transporters. FEBS Lett. 1997;402(1):1– 3.
4. 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;19:47– 63.
5. Hattersley AT and Ashcroft FM. Activating mutations in Kir6.2 and neonatal diabetes: new clinical syndromes, new scientific insights, and new therapy. Diabetes.2005;54(9):2503– 2513.
6. Gloyn AL, Diatloff-Zito C, Edghill EL et al. KCNJ11 activating mutations are associated with developmental delay, epilepsy and neonatal diabetes syndrome and other neurological features. Eur J Hum Genet EJHG Leiden.2006;14(7):824– 30.
7. Flanagan SE, Patch AM, Mackay DJG et al. Mutations in ATP-Sensitive K+ Channel Genes Cause Transient Neonatal Diabetes and Permanent Diabetes in Childhood or Adulthood. Diabetes N Y. 2007;56(7): 1930– 7.
8. D’Amato E, Tammaro P, Craig TJet al. Variable phenotypic spectrum of diabetes mellitus in a family carrying a novel KCNJ11 gene mutation. Diabet Med. 2008;25(6):651– 656.
9. Ashcroft FM. ATP-sensitive K+ channels and disease: from molecule to malady. Am J Physiol-Endocrinol Metab. 2007;293(4):E880– E889.
10.Flanagan SE, Edghill EL, Gloyn AL et al. Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype. Diabetologia. 2006;49(6):1190– 1197.