Genetics of monogenic forms of diabetes

Czech version

Authors: J. Staníkihash3ihash6 ^{1, 2 1, 4 1, 4}
Authors‘ workplace: DIABGENE & Laboratórium diabetu a porúch metabolizmu, Ústav experimentálnej endokrinológie SAV Bratislava, Slovenská republika, riaditeľ prof. MUDr. Iwar Klimeš, DrSc. ¹; Detské diabetologické centrum SR pri I. detskej klinike LF UK a DFNsP Bratislava, Slovenská republika, prednostka doc. MUDr. Oľga Červeňová, CSc. ²; I. detská klinika LF UK a DFNsP Bratislava, Slovenská republika, prednostka doc. MUDr. Oľga Červeňová, CSc. ³; Molekulárno-medicínske centrum SAV Bratislava, Slovenská republika, riaditeľ MUDr. Richard Imrich, CSc. ⁴
Published in: Vnitř Lék 2011; 57(11): 937-945
Category: Birthday

Overview

Monogenic diabetes mellitus is a type of diabetes, where genetics without any other factors is strong enough to cause the disease. According to the clinical features monogenic diabetes can be divided to the mild familial early onset diabetes, familial fasting hyperglycemia, diabetes with extrapancreatic features and neonatal diabetes mellitus. During the last several years the number of genes causing monogenic diabetes has continuously increased. The clinical picture of the monogenic diabetes is very heterogeneous, thus DNA analysis is required for identification of the diabetes etiology, which influences also the choice of treatment. This article is an overview of current knowledge on monogenic diabetes, focusing at the clinically and epidemiologically most important forms.

Key words:
monogenic diabetes mellitus – MODY – neonatal diabetes – DNA analysis

Sources

1. Hattersley A, Bruining J, Shield J et al. The diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes 2009; 10 (Suppl 12): 33–42.

2. Ellard S, Bellanné-Chantelot C, Hattersley AT. European Molecular Genetics Quality Network (EMQN) MODY group. Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young. Diabetologia 2008; 51: 546–553.

3. Murphy R, Ellard S, Hattersley AT. Clinical implications of a molecular genetic classification of monogenic beta-cell diabetes. Nat Clin Pract Endocrinol Metab 2008; 4: 200–213.

4. Vaxillaire MDP, Bonnefond A, Froguel P. Breakthroughs in monogenic diabetes genetics: from pediatric forms to young adulthood diabetes. Pediatr Endocrinol Rev 2009; 6: 405–417.

5. Pruhova S, Dusatkova P, Sumnik Z et al. Glucokinase diabetes in 103 families from a country-based study in the Czech Republic: geographically restricted distribution of two prevalent GCK mutations. Pediatr Diabetes 2010; 11: 529–535.

6. Dusatkova P, Vesela K, Pruhova S et al. Lack of PAX4 mutations in 53 Czech MODYX families. Diabet Med 2010; 27: 1459–1460.

7. Ellard S, Colclough K. Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha (HNF1A) and 4 alpha (HNF4A) in maturity-onset diabetes of the young. Hum Mutat 2006; 27: 854–869.

8. Vesterhus M, Haldorsen IS, Raeder H et al. Reduced pancreatic volume in hepatocyte nuclear factor 1A-maturity-onset diabetes of the young. J Clin Endocrinol Metab 2008; 93: 3505–3509.

9. Katra B, Klupa T, Skupien J et al. Dipeptidyl peptidase-IV inhibitors are efficient adjunct therapy in HNF1A maturity-onset diabetes of the young patients – report of two cases. Diabetes Technol Ther 2010; 12: 313–316.

10. Nyunt O, Wu JY, McGown IN et al. Investigating maturity onset diabetes of the young. Clin Biochem Rev 2009; 30: 67–74.

11. Pinés Corrales PJ, López Garrido MP, Aznar Rodríguez S et al. Clinical differences between patients with MODY-3, MODY-2 and type 2 diabetes mellitus with I27L polymorphism in the HNF1alpha gene. Endocrinol Nutr 2010; 57: 4–8.

12. Pearson ER, Boj SF, Steele AM et al. Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene. PLoS Med 2007; 4: e118.

13. Dusatkova P, Pruhova S, Sumnik Z et al. HNF1A mutation presenting with fetal macrosomia and hypoglycemia in childhood prior to onset of overt diabetes. J Pediatr Endocrinol Metab 2011; 24: 377–379.

14. Shepherd M, Shields B, Ellard S et al. A genetic diagnosis of HNF1A diabetes alters treatment and improves glycaemic control in the majority of insulin-treated patients. Diabet Med 2009; 26: 437–441.

15. Bazalova Z, Rypackova B, Broz J et al. Three novel mutations in MODY and its phenotype in three different Czech families. Diabetes Res Clin Pract 2010; 88: 132–138.

16. Gonsorcikova L, Pruhova S, Cinek O et al. Autosomal inheritance of diabetes in two families characterized by obesity and a novel H241Q mutation in NEUROD1. Pediatr Diabetes 2008; 9: 367–372.

17. 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 USA 2005; 102: 4807–4812.

18. Plengvidhya N, Kooptiwut S, Songtawee N et al. PAX4 mutations in Thais with maturity onset diabetes of the young. J Clin Endocrinol Metab 2007; 92: 2821–2826.

19. Shields BM, Hicks S, Shepherd MH et al. Maturity-onset diabetes of the young (MODY): how many cases are we missing? Diabetologia 2010; 53: 2504–2508.

20. Osbak KK, Colclough K, Saint-Martin C et al. Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia. Hum Mutat 2009; 30: 1512–1526.

21. Gasperikova D, Tribble ND, Stanik J et al. Identification of a novel beta-cell glucokinase (GCK) promoter mutation (–71G>C) that modulates GCK gene expression through loss of allele-specific Sp1 binding causing mild fasting hyperglycemia in humans. Diabetes 2009; 58: 1929–1935.

22. Iynedjian PB. Molecular physiology of mammalian glucokinase. Cell Mol Life Sci 2009; 66: 27–42.

23. Gloyn AL, van de Bunt M, Stratton IM et al. Prevalence of GCK mutations in individuals screened for fasting hyperglycaemia. Diabetologia 2009; 52: 172–174.

24. Codner E, Rocha A, Deng L et al. Mild fasting hyperglycemia in children: high rate of glucokinase mutations and some risk of developing type 1 diabetes mellitus. Pediatr Diabetes 2009; 10: 382–388.

25. Martin D, Bellanné-Chantelot C, Deschamps I et al. Long-term follow-up of oral glucose tolerance test-derived glucose tolerance and insulin secretion and insulin sensitivity indexes in subjects with glucokinase mutations (MODY2). Diabetes Care 2008; 31: 1321–1323.

26. Cuesta-Muñoz AL, Tuomi T, Cobo--Vuilleumier N et al. Clinical heterogeneity in monogenic diabetes caused by mutations in the glucokinase gene (GCK-MODY). Diabetes Care 2010; 33: 290–292.

27. Feigerlova E, Pruhova S, Dittertova L et al. Aetiological heterogeneity of asymptomatic hyperglycaemia in children and adolescents. Eur J Pediatr 2006; 165: 446–452.

28. Tanaka D, Nagashima K, Sasaki M et al. GCKR mutations in Japanese families with clustered type 2 diabetes. Mol Genet Metab 2011; 102: 453–460.

29. Oram RA, Edghill EL, Blackman J et al. Mutations in the hepatocyte nuclear factor-1beta (HNF1B) gene are common with combined uterine and renal malformations but are not found with isolated uterine malformations. Am J Obstet Gynecol 2010; 203: 364 e1–e5.

30. Laloi-Michelin M, Meas T, Ambonville C et al. Mitochondrial Diabetes French Study Group. The clinical variability of maternally inherited diabetes and deafness is associated with the degree of heteroplasmy in blood leukocytes. J Clin Endocrinol Metab 2009; 94: 3025–3030.

31. Vincent-Desplanques D, Faivre-Defrance F, Wémeau JL et al. Monogenic severe insulin resistance syndromes. Rev Med Interne 2005; 26: 866–873.

32. Suliman SG, Stanik J, McCulloch LJ et al. Severe insulin resistance and intrauterine growth deficiency associated with haploinsufficiency for INSR and CHN2: new insights into synergistic pathways involved in growth and metabolism. Diabetes 2009; 58: 2954–2961.

33. Musso C, Cochran E, Moran SA et al. Clinical course of genetic diseases of the insulin receptor (type A and Rabson-Mendenhall syndromes): a 30-year prospective. Medicine (Baltimore) 2004; 83: 209–222.

34. Johansson BB, Torsvik J, Bjørkhaug L et al. Diabetes and Pancreatic Exocrine Dysfunction Due to Mutations in the Carboxyl Ester Lipase Gene-Maturity Onset Diabetes of the Young (CEL-MODY): a protein misfolding disease. J Biol Chem 2011; 286: 34593–34605.

35. Raeder H, Johansson S, Holm PI et al. Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction. Nat Genet 2006; 38: 54–62.

36. Torsvik J, Johansson S, Johansen A et al. Mutations in the VNTR of the carboxyl-ester lipase gene (CEL) are a rare cause of monogenic diabetes. Hum Genet 2010; 127: 55–64.

37. Borowiec M, Liew CW, Thompson R et al. Mutations at the BLK locus linked to maturity onset diabetes of the young and beta-cell dysfunction. Proc Natl Acad Sci USA 2009; 106: 14460–14465.

38. Garg A. Acquired and inherited lipodystrophies. N Engl J Med 2004; 350: 1220–1234.

39. Garg A, Misra A. Lipodystrophies: rare disorders causing metabolic syndrome. Endocrinol Metab Clin North Am 2004; 33: 305–331.

40. Gomes KB, Fernandes AP, Ferreira AC et al. Mutations in the seipin and AGPAT2 genes clustering in consanguineous families with Berardinelli-Seip congenital lipodystrophy from two separate geographical regions of Brazil. J Clin Endocrinol Metab 2004; 89: 357–361.

41. d‘Annunzio G, Minuto N, D‘Amato E et al. Wolfram syndrome (diabetes insipidus, diabetes, optic atrophy, and deafness): clinical and genetic study. Diabetes Care 2008; 31: 1743–1745.

42. Domènech E, Gómez-Zaera M, Nunes V. Study of the WFS1 gene and mitochondrial DNA in Spanish Wolfram syndrome families. Clin Genet 2004; 65: 463–469.

43. Zaidi G, Sahu RP, Zhang L et al. Two novel AIRE mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) among Indians. Clin Genet 2009; 76: 441–448.

44. Polak M, Shield J. Neonatal Diabetes Mellitus – genetic aspects 2004. Pediatr Endocrinol Rev 2004; 2: 193–198.

45. 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: 1034–1042.

46. Polak M. Neonatal diabetes mellitus: insights for more common forms of diabetes. J Clin Endocrinol Metab 2007; 92: 3774–3776.

47. Stanik J, Gasperikova D, Paskova M et al. Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers. J Clin Endocrinol Metab 2007; 92: 1276–1282.

48. Shield JP, Temple IK, Sabin M et al. An assessment of pancreatic endocrine function and insulin sensitivity in patients with transient neonatal diabetes in remission. Arch Dis Child Fetal Neonatal Ed 2004; 89: F341–F343.

49. Mackay DJ, Boonen SE, Clayton--Smith J et al. A maternal hypomethylation syndrome presenting as transient neonatal diabetes mellitus. Hum Genet 2006; 120: 262–269.

50. Stanik J, Lethby M, Flanagan SE et al. Coincidence of a novel KCNJ11 missense variant R365H with a paternally inherited 6q24 duplication in a patient with transient neonatal diabetes. Diabetes Care 2008; 31: 1736–1737.

51. Temple IK, Shield JP. Transient neonatal diabetes, a disorder of imprinting. J Med Genet 2002; 39: 872–875.

52. Mackay DJ, Callaway JL, Marks SM et al. Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57. Nat Genet 2008; 40: 949–951.

53. Bonnefond A, Durand E, Sand O et al. Molecular diagnosis of neonatal diabetes mellitus using next-generation sequencing of the whole exome. PLoS One 2010; 5: e13630.

54. Männikkö R, Flanagan SE, Sim X et al. Mutations of the Same Conserved Glutamate Residue in NBD2 of the Sulfonylurea Receptor 1 Subunit of the KATP Channel Can Result in Either Hyperinsulinism or Neonatal Diabetes. Diabetes 2011; 60: 1813–1822.

55. Hattersley AT, Ashcroft FM. Activating mutations in Kir6.2 and neonatal diabetes: new clinical syndromes, new scientific insights, and new therapy. Diabetes 2005; 54: 2503–2513.

56. Flanagan SE, Patch AM, Mackay DJ et al. Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood. Diabetes 2007; 56: 1930–1937.

57. Bonnefond A, Froguel P, Vaxillaire M. The emerging genetics of type 2 diabetes. Trends Mol Med 2010; 16: 407–416.