Molecular-genetic verification and treatment of neonatal diabetes mellitus related to the defects in ATP-dependent potassium channels: Results of the observation of 9 patients and the first description of ABCC8 gene mutations in Russia

Dedov I.I.

Endocrinology Research Centre

Tikhonovich Iu.V.

Éndokrinologicheskiĭ nauchnyĭ tsentr Minzdravsotsrazvitiia Rossii

E Petriaĭkina E.

Morozovskaia detskaia gorodskaia klinicheskaia bol'nitsa

Rybkina I.G.

Morozovskaia detskaia gorodskaia klinicheskaia bol'nitsa

Volkov I.É.

Rossiĭskaia detskaia klinicheskaia bol'nitsa, Moskva

Stotikova O.V.

Rossiĭskaia detskaia klinicheskaia bol'nitsa, Moskva

Chernykh L.G.

Oblastnaia detskaia klinicheskaia bol'nitsa, Ekaterinburg

Tiul'pakov A.N.

Éndokrinologicheskiĭ nauchnyĭ tsentr, Moskva

Molecular-genetic verification and treatment of neonatal diabetes mellitus related to the defects in ATP-dependent potassium channels: Results of the observation of 9 patients and the first description of ABCC8 gene mutations in Russia

Authors:

Dedov I.I., Tikhonovich Iu.V., E Petriaĭkina E., Rybkina I.G., Volkov I.É., Stotikova O.V., Chernykh L.G., Tiul'pakov A.N.

More about the authors

Journal: Problems of Endocrinology. 2011;57(2): 3‑8

Downloaded: 27

Download PDF (RU)

Contact the author

Table of contents

To cite this article:

Dedov II, Tikhonovich IuV, E Petriaĭkina E, et al. . Molecular-genetic verification and treatment of neonatal diabetes mellitus related to the defects in ATP-dependent potassium channels: Results of the observation of 9 patients and the first description of ABCC8 gene mutations in Russia. Problems of Endocrinology. 2011;57(2):3‑8. (In Russ.)

Close metadata

Introduction of the methods for molecular-genetic analysis into clinical practice has opened up new prospects for both diagnosis and pathogenetically sound therapy of neonatal diabetes mellitus. It is currently known that the overwhelming majority of the cases of diabetes mellitus developing in children during the first six month of life are associated with defects of the genes controlling formation, development, and functional activity of pancreatic beta-cells whereas type 1 diabetes mellitus of autoimmune origin accounts for less than 1% of this pathology. This paper reports the results of a molecular-genetic study of 14 patients presenting with neonatal diabetes mellitus. Nine cases are shown to have developed as a result of mutations in KCNJ11 and ABCC8 genes. ABCC8 mutations are described for the first time in Russia. Analysis of clinical forms of neonatal diabetes mellitus revealed correlation between the type of mutations, clinical features of the disease, and susceptibility of the patients to sulfonylurea drugs.

Keywords:

neonatal diabetes mellitus

ATP-dependent potassium channels

KCNJ11 and ABCC8 genes

glibenclamid

Authors:

Dedov I.I.

Endocrinology Research Centre

Tikhonovich Iu.V.

Éndokrinologicheskiĭ nauchnyĭ tsentr Minzdravsotsrazvitiia Rossii

E Petriaĭkina E.

Morozovskaia detskaia gorodskaia klinicheskaia bol'nitsa

Rybkina I.G.

Morozovskaia detskaia gorodskaia klinicheskaia bol'nitsa

Volkov I.É.

Rossiĭskaia detskaia klinicheskaia bol'nitsa, Moskva

Stotikova O.V.

Rossiĭskaia detskaia klinicheskaia bol'nitsa, Moskva

Chernykh L.G.

Oblastnaia detskaia klinicheskaia bol'nitsa, Ekaterinburg

Tiul'pakov A.N.

Éndokrinologicheskiĭ nauchnyĭ tsentr, Moskva

List of references:

Gloyn A.L., Pearson E.R., Antcliff J.F. et al. Activating mutations in the ATP-sensitive potassium channel subunit Kir6.2 gene are associated with permanent neonatal diabetes. N Engl J Med 2004;350:1838-1849.
Babenko A.P., Polak M., Cavé H. et al. Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. N Engl J Med 2006;355:456-466.
Njolstad P.R., Sovik O., Cuesta-Munoz A. et al. Neonatal diabetes mellitus due to complete glucokinase deficiency. N Engl J Med 2001;344:1588-1592.
Stoffers D.A., Zinkin N.T., Stanojevic V. et al. Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence. Nat Genet 1997;15:106-110.
Taha D., Barbar M., Kanaan H., Williamson Balfe J. Neonatal diabetes mellitus, congenital hypothyroidism, hepatic fibrosis, polycystic kidneys, and congenital glaucoma: a new autosomal recessive syndrome? Am J Med Genet 2003;122A:269-273.
Senee V., Chelala C., Duchatelet S. et al. Mutations in GLIS3 are responsible for a rare syndrome with neonatal diabetes mellitus and congenital hypothyroidism. Nat Genet 2006;38:6:682-687.
Edghill E.L., Bingham C., Slingerland A.S. et al. Hepatocyte nuclear factor-1 beta mutations cause neonatal diabetes and intrauterine growth retardation: support for a critical role of HNF-1β in human pancreatic development. Diabet Med 2006;23:1301-1306.
Hoveyda N., Shield J.P., Garrett C. et al. Neonatal diabetes mellitus and cerebellar hypoplasia/agenesis: report of a new recessive syndrome. J Med Genet 1999;36:700-704.
Sellick G.S., Barker K.T., Stolte-Dijkstra I. et al. Mutations in PTF1A cause pancreatic and cerebellar agenesis. Nat Genet 2006;36:12:1301-1305.
Stoy J., Edghill E.L., Flanagan S.E. et al. Insulin gene mutations as a cause of permanent neonatal diabetes. Proc Natl Acad Sci USA 2007;104:15040-15044.
Delepine M., Nicolino M., Barret T. et al. EIF2AK3, encoding translation initiation factor-2 alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome. Nat Genet 2000;25:406-409.
Bennett C.L., Yoshioka R., Kiyosawa H. et al. X-Linked syndrome of polyendocrinopathy, immune dysfunction, and diarrhea maps to Xp11.23-Xq13.3. Am J Hum Genet 2000;66:461-468.
Aguilar-Bryan L., Bryan J. Neonatal diabetes mellitus. Endocr Rev 2008;29:3:265-291.
Flanagan S.E., Edghill E.L., Gloun A.L. et al. Mutations in KCNJ11, which encodes Kir 6.2, are a common case of diabetes diagnosed in the first 6 months of life, with the genotype determited by genotype. Diabetologia 2006;49:1190-1197.
Balabolkin M.I., Klebanova E.M. Primenenie glibenklamida i metformina v vide preparata kombinirovannogo deistviya dlya lecheniya sakharnogo diabeta 2-go tipa. Rus med zhurn 2006;4:13:977-981.
Pearson E.R., Flechtner I., Njolstad P.R. et al. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir 6.2 mutations. N Engl J Med 2006;355:467-477.
Rafiq M., Flanagan S.E., Patch A.M. et al. Effective treatment with oral sulfonylureas in patients with diabetes mellitus to sulfonyrea receptor 1(SUR1) mutations. Diabet Care 2007;31:204-209.
Malievskii O.A., Nurmukhamedova D.S., Basharova R.V. Opyt lecheniya neonatal'nogo sakharnogo diabeta, obuslovlennogo mutatsiei gena KCNJ11, kodiruyushchego sub''edinitsu Kir 6.2, preparatami sul'fonilmocheviny. Vserossiiskaya nauchno-prakticheskaya konferentsiya "Zadachi detskoi endokrinologii v realizatsii Natsional'nogo proekta "Zdorov'e": Materialy. M 2008;73.
Emel'yanov A.O., Petryaikina E.E., Kuraeva T.L. i dr. Vozmozhnosti effektivnoi terapii neonatal'nogo sakharnogo diabeta preparatami sul'fonilmocheviny pri nalichii mutatsii v gene KCNJ11: sobstvennye nablyudeniya. Sakharnyi diabet 2009;3:86-89.
Kuraeva T.L., Emel'yanov A.O. Klinicheskaya i geneticheskaya geterogennost' neonatal'nogo sakharnogo diabeta. Sakharnyi diabet 2009;3:10-15.
Den Dunnen J.T., Antonarakis S.E. Nomenclature for the description of human sequence variations. Hum Genet 2001;109:1:121-124.
Shyng S.L., Nichols C.G. Octameric stoichiometry of the KATP channel complex. J Gen Physiol 1997;110:655-664.
Higgins C.F., Linton K.J. The ATP switch model for ABC transporters. Nat Struct Mol Biol 2004;11:918-926.
Babenko A.P., Gonzalez G., Bryan J. The N-terminus of KIR6.2 limits spontaneous bursting and modulates the ATP-inhibition of KATP channels. Biochem Biophys Res Commun 1999;255:231-238.
Chan K.W., Zhang H., Logothetis D.E. N-terminal transmembrane domain of the SUR controls trafficking and gating of Kir6 channel subunits. EMBO J 2003;22:3833-3843.
Bryan J., Vila-Carriles W.H., Zhao G. et al. Toward linking structure with function in ATP-sensitive K+ channels. Diabetes 2004;53:Suppl 3:S104-S112.
Gribble F.M., Ashcroft F.M. Differential sensitivity of β-cell and extrapancreatic K(ATP) channels to gliclazide. Diabetologia 1999;42:845-848.
Koster J.C., Cadario F., Peruzzi C. et al. The G53D mutation in Kir6.2 (KCNJ11) is associated with neonatal diabetes and motor dysfunction in adulthood that is improved with sulfonylurea therapy. J Clin Endocrinol Metab 2008;93:1054-1061.
Aguilar-Bryan L., Nichols C.G., Wechsler S.W. et al. Cloning of the beta cell high affinity sulfonylurea receptor: a regulator of insulin secretion. Science 1995;268:423-426.
Flanagan S.E., Clauin S., Bellanné-Chantelot C. et al. Update of mutations in the genes encoding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism. Hum Mutat 2009;30:170-180.
Ellard S., Flanagan S.E., Girard C.A. et al. Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects. Am J Hum Genet 2007;81:375-382.
Stoy J., Greeley S.A., Paz V.P. et al. Diagnosis and treatment of neonatal diabetes: an United States experience. Pediat Diabetes 2008;9:450-459.
Masia R., De Leon D.D., MacMullen C. et al. A mutation in the TMD0-L0 region of SUR1 (L225P) causes permanent neonatal diabetes mellitus (PNDM). Diabetes 2007;56:1357-1362.
Proks P., Arnold A.L., Bruining J. et al. A heterozygous activating mutation in the sulphonylurea receptor SUR1 (ABCC8) causes neonatal diabetes. Hum Mol Genet 2006;15:1793-1800.

Close metadata