Monogenic models: What have the single gene disorders taught us?

Current Diabetes Reports

Volumn 12, Issue 6, 2012, Pages 659-666

  Klupa, Tomasz ^a,b   Skupien, Jan ^c   Malecki, Maciej T ^a,b  

^a JAGIELLONIAN UNIVERSITY   (Poland)

^b UNIVERSITY HOSPITAL IN KRAKOW   (Poland)

^c HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Gene; Monogenic diabetes; Mutation; Pharmacogenetics

Indexed keywords

GLIBENCLAMIDE; GLICLAZIDE; GLUCOSE; GLUCOSE TRANSPORTER 2; HEPATOCYTE NUCLEAR FACTOR 1ALPHA; INSULIN; INWARDLY RECTIFYING POTASSIUM CHANNEL; METFORMIN; ORAL ANTIDIABETIC AGENT; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PROTEIN KINASE B BETA; SULFONYLUREA;

ABCC8 GENE; AKT2 GENE; ANTIDIABETIC ACTIVITY; DRUG EFFICACY; DRUG RESPONSE; GCK GENE; GENE; GENE IDENTIFICATION; GENE MUTATION; GENETIC ASSOCIATION; GENETIC RISK; GENETIC SCREENING; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; GLUT2 GENE; HNF1A GENE; HNF4A GENE; HUMAN; HYPOGLYCEMIA; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN RESISTANCE; INSULIN SENSITIVITY; KCNJ11 GENE; MEDICAL RESEARCH; MONOGENIC DISORDER; NEWBORN DIABETES MELLITUS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PATHOGENESIS; PERSONALIZED MEDICINE; PHARMACOGENOMICS; PPARG GENE; REVIEW;

ATP-BINDING CASSETTE TRANSPORTERS; DIABETES MELLITUS, TYPE 1; DIABETES MELLITUS, TYPE 2; FEMALE; GENETIC PREDISPOSITION TO DISEASE; GENETIC TESTING; GENOTYPE; HEPATOCYTE NUCLEAR FACTOR 1-ALPHA; HUMANS; HYPERGLYCEMIA; HYPOGLYCEMIC AGENTS; MALE; MODELS, BIOLOGICAL; MUTATION; PHARMACOGENETICS; POTASSIUM CHANNELS, INWARDLY RECTIFYING; RECEPTORS, DRUG; SULFONYLUREA COMPOUNDS;

EID: 84870663099     PISSN: 15344827     EISSN: 15390829     Source Type: Journal    
DOI: 10.1007/s11892-012-0325-0     Document Type: Review

References (75)

1. National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes. 1979;28:1039-57.
2. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 2003;(SUPPL. 1):5-20.
3. Tattersall RB, Fajans SS. A difference between the inheritance of classical juvenile-onset and maturity-onset type diabetes of young people. Diabetes. 1975;24:44-53.
4. Hattersley AT. Maturity-onset diabetes of the young: clinical heterogeneity explained by genetic heterogeneity. Diabet Med. 1998;15:15-24.
5. Fajans SS, Bell GI, Polonsky KS. Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young. N Engl J Med. 2001;345:971-80.
6. McCarthy MI, Hattersley AT. Molecular diagnostics in monogenic and multifactorial forms of type 2 diabetes. Expert Rev Mol Diagn. 2001;1:403-12.
7. Hattersley AT. Molecular genetics goes to the diabetes clinic. Clin Med. 2005;5:476-81.
8. Malecki MT, Mlynarski W, Skupien J. Can geneticists help clinicians to understand and treat non-Autoimmune diabetes? Diabetes Res Clin Pract. 2008;82 SUPPL. 2:S83-93.
9. Peltonen L, McKusick VA. Genomics and medicine. Dissecting human disease in the postgenomic era. Science. 2001;291:1224-9.
10. Porter JR, Barrett TG. Monogenic syndromes of abnormal glucose homeostasis: clinical review and relevance to the understanding of the pathology of insulin resistance and beta cell failure. J Med Genet. 2005;42:893-902.
11. Rubio-Cabezas O, Klupa T, Malecki MT. CEED3 Consortium Permanent neonatal diabetes mellitus-the importance of diabetesdifferential diagnosis in neonates and infants. Eur J Clin Invest. 2011;41:323-33.
12. Malecki MT. The search for undiagnosed MODY patients: what is the next step? Diabetologia. 2010;53:2465-7.
13. Yoshimasa Y, Seino S, Whittaker J, et al. Insulin-resistant diabetes due to a point mutation that prevents insulin proreceptor processing. Science. 1988;240:784-7.
14. Stoffel M, Patel P, Lo YM, et al. Missense glucokinase mutation in maturity-onset diabetes of the young and mutation screening in late-onset diabetes. Nat Genet. 1992;2:153-6.
15. Yamagata K, Furuta H, Oda N, et al. Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1). Nature. 1996;384:458-60.
16. Yamagata K, Oda N, Kaisaki PJ, et al. Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3). Nature. 1996;384:455-8.
17. Horikawa Y, Iwasaki N, Hara M, et al. Mutation in hepatocyte nuclear factor-1 beta gene (TCF2) associated with MODY. Nat Genet. 1997;17:384-5.
18. Stoffers DA, Ferrer J, Clarke WL, et al. Early-onset type-II diabetes mellitus (MODY4) linked to IPF1. Nat Genet. 1997;17:138-9.
19. Malecki MT, Jhala US, Antonellis A, et al. Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Nat Genet. 1999;23:323-8.
20. Altshuler D, Hirschhorn JN, Klannemark M, et al. The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet. 2000;26:76-80.
21. Hani EH, Boutin P, Durand E, et al. Missense mutations in the pancreatic islet beta cell inwardly rectifying K + channel gene (KIR6.2/BIR): a meta-Analysis suggests a role in the polygenic basis of Type II diabetes mellitus in Caucasians. Diabetologia. 1998;41:1511-5.
22. Botstein D, Risch N. Discovering genotypes underlying human phenotypes: past successes for mendelian disease, future approaches for complex disease. Nat Genet. 2003;33(SUPPL.):228- 37.
23. Turner RC, Hattersley AT, Shaw JT, et al. Type II diabetes: clinical aspects of molecular biological studies. Diabetes. 1995;44:1-10.
24. Grant SF, Thorleifsson G, Reynisdottir I, et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet. 2006;38:320-3.
25. McCarthy MI, Abecasis GR, Cardon LR, et al. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet. 2008;9:356-69.
26. Visscher PM, Brown MA, McCarthy MI, et al. Five years of GWAS discovery. Am J Hum Genet. 2012;90:7-24.
27. Vaxillaire M, Froguel P. Monogenic diabetes in the young, pharmacogenetics and relevance to multifactorial forms of type 2 diabetes. Endocr Rev. 2008;29:254-64.
28. Lango H, Palmer CN, Morris AD, et al. Assessing the combined impact of 18 common genetic variants of modest effect sizes on type 2 diabetes risk. Diabetes. 2008;57:3129-35.
29. Meigs JB, Shrader P, Sullivan LM, et al. Genotype score in addition to common risk factors for prediction of type 2 diabetes. N Engl J Med. 2008;359:2208-19.
30. Maher B. Personal genomes: the case of the missing heritability. Nature. 2008;456:18-21.
31. Ku CS, Cooper DN, Polychronakos C, et al. Exome sequencing: dual role as a discovery and diagnostic tool. Ann Neurol. 2012;71:5-14.
32. Majewski J, Schwartzentruber J, Lalonde E, et al. What can exome sequencing do for you? J Med Genet. 2011;48:580-9.
33. Cirulli ET, Goldstein DB. Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nat Rev Genet. 2010;11:415-25. In this review paper, the evidence for an important role of rare gene variants of major effect in common diseases and outline discovery strategies for their identification are summarized.
34. Matschinsky FM. Glucokinase as glucose sensor and metabolic signal generator in pancreatic β-cell and hepatocytes. Diabetes. 1990;30:647-752.
35. McCulloch LJ, van de Bunt M, Braun M, et al. GLUT2 (SLC2A2) is not the principal glucose transporter in human pancreatic beta cells: implications for understanding genetic association signals at this locus. Mol Genet Metab. 2011;104:648-53.
36. Ashcroft FM, Rorsman P. Diabetes mellitus and the β cell: the last ten years. Cell. 2012;148:1160-71.
37. Santer R, Schneppenheim R, Dombrowski A, et al. Mutations in GLUT2, the gene for the liver-type glucose transporter, in patients with Fanconi-Bickel syndrome. Nat Genet. 1997;17:324-6.
38. Yoo HW, Shin YL, Seo EJ, et al. Identification of a novel mutation in the GLUT2 gene in a patient with Fanconi-Bickel syndrome presenting with neonatal diabetes mellitus and galactosaemia. Eur J Pediatr. 2002;161:351-3.
39. Sansbury FH, Flanagan SE, Houghton JA, et al. SLC2A2 mutations can cause neonatal diabetes, suggesting GLUT2 may have a role in human insulin secretion. Diabetologia. 2012;55:2381-5.
40. Byrne MM, Sturis J, Clément K, et al. Insulin secretory abnormalities in subjects with hyperglycemia due to glucokinase mutations. J Clin Invest. 1994;93:1120-30.
41. Njølstad PR, Søvik O, Cuesta-Muñoz A, et al. Neonatal diabetes mellitus due to complete glucokinase deficiency. N Engl J Med. 2001;344:1588-92.
42. van den Ouweland JM, Lemkes HH, RuitenbeekW, et al. Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. Nat Genet. 1992;1:368-71.
43. Guillausseau PJ, Massin P, Dubois-LaForgue D, et al. Maternally inherited diabetes and deafness: a multicenter study. Ann Intern Med. 2001;134:721-8.
44. McTaggart JS, Clark RH, Ashcroft FM. The role of the KATP channel in glucose homeostasis in health and disease: more than meets the islet. J Physiol. 2010;588:3201-9.
45. Babenko AP, Polak M, Cavé H, et al. Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. N Engl J Med. 2006;355:456-66.
46. 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;104:15040-4.
47. Edghill EL, Flanagan SE, Patch AM, et al. Insulin mutation screening in 1044 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;57:1034-42.
48. Servitja JM, Ferrer J. Transcriptional networks controlling pancreatic development and beta cell function. Diabetologia. 2004;47:597-613.
49. Donohue WL, Uchida I. Leprechaunism: a euphemism for a rare familial disorder. J Pediatr. 1954;45:505-19.
50. Rabson SM, Mendenhall EN. Familial hypertrophy of pineal body, hyperplasia of adrenal cortex and diabetes mellitus; report of 3 cases. Am J Clin Pathol. 1956;26:283-90.
51. Krook A, Brueton L, O'Rahilly S. Homozygous nonsense mutation in the insulin receptor gene in infant with leprechaunism. Lancet. 1993;342:277-8.
52. Kadowaki T, Kadowaki H, Accili D, et al. Substitution of lysine for asparagine at position 15 in the alpha-subunit of the human insulin receptor. A mutation that impairs transport of receptors to the cell surface and decreases the affinity of insulin binding. J Biol Chem. 1990;265:19143-50.
53. Odawara M, Kadowaki T, Yamamoto R, et al. Human diabetes associated with a mutation in the tyrosine kinase domain of the insulin receptor. Science. 1989;245:66-8.
54. George S, Rochford JJ, Wolfrum C, et al. A family with severe insulin resistance and diabetes due to a mutation in AKT2. Science. 2004;304:1325-8.
55. Barroso I, Gurnell M, Crowley VE, et al. Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature. 1999;402:880-3.
56. Shackleton S, Lloyd DJ, Jackson SN, et al. LMNA, encoding lamin A/C, is mutated in partial lipodystrophy. Nat Genet. 2000;24:153-6.
57. Gribble FM, Reimann F. Sulphonylurea action revisited: the postcloning era. Diabetologia. 2003;46:875-91.
58. Sovik O, Njolstad P, Folling I, et al. Hyperexcitability to sulphonylurea in MODY3. Diabetologia. 1998;41:607-8.
59. Pearson ER, Liddell WG, Shepherd M, et al. Sensitivity to sulphonylureas in patients with hepatocyte nuclear factor-1alpha gene mutations: evidence for pharmacogenetics in diabetes. Diabet Med. 2000;17:543-5.
60. Pearson ER, Starkey BJ, Powell RJ, et al. Genetic cause of hyperglycaemia and response to treatment in diabetes. Lancet. 2003;362:1275-81. This clinical trial shows that the cause of hyperglycaemia changes the response to hypoglycaemic drugs and HNFA MODY has marked sulphonylurea sensitivity.
61. Pearson ER, Pruhova S, Tack CJ, et al. Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4alpha mutations in a large European collection. Diabetologia. 2005;48:878-85.
62. Page RC, Hattersley AT, Levy JC, et al. Clinical characteristics of subjects with a missense mutation in glucokinase. Diabet Med. 1995;12:209-17.
63. Maassen JA, 'T Hart LM, Van Essen E, et al. Mitochondrial diabetes: molecular mechanisms and clinical presentation. Diabetes. 2004;53 SUPPL. 1:103-9.
64. Sagen JV, Raeder H, Hathout E, et al. Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy. Diabetes. 2004;53:2713-8.
65. Vaxillaire M, Populaire C, Busiah K, et al. Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients. Diabetes. 2004;53:2719-22.
66. Massa O, Iafusco D, D'Amato E, et al. KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes. Hum Mutat. 2005;25:22-7.
67. Pearson ER, Flechtner I, Njolstad PR, et al. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. Engl J Med. 2006;355:467-77. This large clinical observation shows that sulfonylurea therapy is safe for patients with PNDM caused by KCNJ11 mutations and is probably more effective than insulin therapy.
68. Tonini G, Bizzarri C, Bonfanti R, et al. Sulfonylurea treatment outweighs insulin therapy in short-term metabolic control of patients with permanent neonatal diabetes mellitus due to activating mutations of the KCNJ11 (KIR6.2) gene. Diabetologia. 2006;49:2210-3.
69. Malecki MT, Skupien J, Klupa T, et al. Transfer to sulphonylurea therapy in adult subjects with permanent neonatal diabetes due to KCNJ11-Activating mutations: evidence for improvement in insulin sensitivity. Diabetes Care. 2007;30:147-9.
70. Mlynarski W, Tarasov AI, Gach A, et al. Sulfonylurea improves CNS function in a case of intermediate DEND syndrome caused by a mutation in KCNJ11. Nat Clin Pract Neurol. 2007;3:640-5.
71. Sesti G, Laratta E, Cardellini M, et al. The E23K variant of KCNJ11 encoding the pancreatic beta-cell adenosine 5'-triphosphate-sensitive potassium channel subunit Kir6.2 is associated with an increased risk of secondary failure to sulfonylurea in patients with type 2 diabetes. J Clin Endocrinol Metab. 2006;91:2334-9.
72. Pearson ER, Donnelly LA, Kimber C, et al. Variation in TCF7L2 influences therapeutic response to sulfonylureas: a GoDARTs study. Diabetes. 2007;56:2178-82.
73. Feng Y, Mao G, Ren X, et al. Ser1369Ala variant in sulfonylurea receptor gene ABCC8 is associated with antidiabetic efficacy of gliclazide in Chinese type 2 diabetic patients. Diabetes Care. 2008;31:1939-44.
74. Holstein A, Hahn M, Stumvoll M, et al. The E23K variant of KCNJ11 and the risk for severe sulfonylurea-induced hypoglycemia in patients with type 2 diabetes. Horm Metab Res. 2009;41:387-90.
75. Hamming KS, Soliman D, Matemisz LC, et al. Coexpression of the type 2 diabetes susceptibility gene variants KCNJ11 E23K and ABCC8 S1369A alter the ATP and sulfonylurea sensitivities of the ATP-sensitive K(+) channel. Diabetes. 2009;58:2419-24.