ISPAD Clinical Practice Consensus Guidelines 2018: The diagnosis and management of monogenic diabetes in children and adolescents

Pediatric Diabetes

Volumn 19, Issue , 2018, Pages 47-63

  Hattersley, Andrew T ^a   Greeley, Siri A W ^b   Polak, Michel ^c   Rubio Cabezas, Oscar ^d   Njølstad, Pål R ^e,f   Mlynarski, Wojciech ^g   Castano, Luis ^h   Carlsson, Annelie ⁱ   Raile, Klemens ^j   Chi, Dung V ^k,l   Ellard, Sian ^a   Craig, Maria E ^m,n  

^a UNIVERSITY OF EXETER MEDICAL SCHOOL   (United Kingdom)

^b UNIVERSITY OF CHICAGO   (United States)

^c HÔPITAL NECKER ENFANTS MALADES   (France)

^d HOSPITAL INFANTIL UNIVERSITARIO NIÑO JESÚS   (Spain)

^e UNIVERSITY OF BERGEN   (Norway)

^f HAUKELAND UNIVERSITY HOSPITAL   (Norway)

^g MEDICAL UNIVERSITY OF LODZ   (Poland)

^h BIOCRUCES BIZKAIA HEALTH RESEARCH INSTITUTE   (Spain)

ⁱ LUND UNIVERSITY HOSPITAL   (Sweden)

^j CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^k NATIONAL HOSPITAL OF PEDIATRICS   (Viet Nam)

^l HANOI MEDICAL UNIVERSITY   (Viet Nam)

^m UNIVERSITY OF SYDNEY   (Australia)

ⁿ UNIVERSITY OF NEW SOUTH WALES   (Australia)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ADOLESCENT; CHILD; CLASSIFICATION; CLINICAL PRACTICE; CONSENSUS; DIABETES MELLITUS; ENDOCRINE SYSTEM EXAMINATION; ENDOCRINOLOGY; GENETICS; HUMAN; INTERNATIONAL COOPERATION; MEDICAL SOCIETY; MOLECULAR DIAGNOSIS; NEWBORN; NEWBORN SCREENING; ORGANIZATION AND MANAGEMENT; PATIENT SELECTION; PEDIATRICS; PRACTICE GUIDELINE; PROCEDURES; STANDARDS;

ADOLESCENT; CHILD; CONSENSUS; DIABETES MELLITUS; DIAGNOSTIC TECHNIQUES, ENDOCRINE; ENDOCRINOLOGY; HUMANS; INFANT, NEWBORN; INTERNATIONAL COOPERATION; MOLECULAR DIAGNOSTIC TECHNIQUES; NEONATAL SCREENING; PATIENT SELECTION; PEDIATRICS; PRACTICE PATTERNS, PHYSICIANS'; SOCIETIES, MEDICAL;

EID: 85054101031     PISSN: 1399543X     EISSN: 13995448     Source Type: Journal    
DOI: 10.1111/pedi.12772     Document Type: Article

References (216)

1. Fajans SS, Bell GI. MODY: history, genetics, pathophysiology, and clinical decision making. Diabetes Care. 2011;34(8):1878-1884
2. Tattersall R. Maturity-onset diabetes of the young: a clinical history. Diabet Med. 1998;15(1):11-14
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(1):44-53
4. Tattersall RB. Mild familial diabetes with dominant inheritance. Q J Med. 1974;43(170):339-357
5. 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(4):200-213
6. 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
7. Bellanné-Chantelot C, Clauin S, Chauveau D, et al. Large genomic rearrangements in the hepatocyte nuclear factor-1beta (TCF2) gene are the most frequent cause of maturity-onset diabetes of the young type 5. Diabetes. 2005;54(11):3126-3132
8. 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
9. Møller AM, Dalgaard LT, Pociot F, Nerup J, Hansen T, Pedersen O. Mutations in the hepatocyte nuclear factor-1alpha gene in Caucasian families originally classified as having type I diabetes. Diabetologia. 1998;41(12):1528-1531
10. Lambert AP, Ellard S, Allen LI, et al. Identifying hepatic nuclear factor 1alpha mutations in children and young adults with a clinical diagnosis of type 1 diabetes. Diabetes Care. 2003;26(2):333-337
11. Awa WL, Schober E, Wiegand S, et al. Reclassification of diabetes type in pediatric patients initially classified as type 2 diabetes mellitus: 15 years follow-up using routine data from the German/Austrian DPV database. Diabetes Res Clin Pract. 2011;94:463-467
12. 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
13. Fendler W, Borowiec M, Baranowska-Jazwiecka A, et al. Prevalence of monogenic diabetes amongst Polish children after a nationwide genetic screening campaign. Diabetologia. 2012;55(10):2631-2635
14. Irgens HU, Molnes J, Johansson BB, et al. Prevalence of monogenic diabetes in the population-based Norwegian Childhood Diabetes Registry. Diabetologia. 2013;56(7):1512-1519
15. Pihoker C, Gilliam LK, Ellard S, et al. Prevalence, characteristics and clinical diagnosis of maturity onset diabetes of the young due to mutations in HNF1A, HNF4A, and glucokinase: results from the SEARCH for Diabetes in Youth. J Clin Endocrinol Metab. 2013;98(10):4055-4062
16. Johansson BB, Irgens HU, Molnes J, et al. Targeted next-generation sequencing reveals MODY in up to 6.5% of antibody-negative diabetes cases listed in the Norwegian Childhood Diabetes Registry. Diabetologia. 2017;60(4):625-635
17. Delvecchio M, Mozzillo E, Salzano G, et al. Monogenic diabetes accounts for 6.3% of cases referred to 15 Italian pediatric diabetes centers during 2007 to 2012. J Clin Endocrinol Metab. 2017;102(6):1826-1834
18. Shepherd M, Shields B, Hammersley S, et al. Systematic population screening, using biomarkers and genetic testing, identifies 2.5% of the U.K. pediatric diabetes population with monogenic diabetes. Diabetes Care. 2016;39(11):1879-1888
19. Bonnefond A, Philippe J, Durand E, et al. Highly sensitive diagnosis of 43 monogenic forms of diabetes or obesity through one-step PCR-based enrichment in combination with next-generation sequencing. Diabetes Care. 2014;37(2):460-467
20. Ellard S, Lango Allen H, De Franco E, et al. Improved genetic testing for monogenic diabetes using targeted next-generation sequencing. Diabetologia. 2013;56(9):1958-1963
21. Gao R, Liu Y, Gjesing AP, et al. Evaluation of a target region capture sequencing platform using monogenic diabetes as a study-model. BMC Genet. 2014;15:13
22. Johansson S, Irgens H, Chudasama KK, et al. Exome sequencing and genetic testing for MODY. PLoS One. 2012;7(5):e38050
23. Alkorta-Aranburu G, Carmody D, Cheng YW, et al. Phenotypic heterogeneity in monogenic diabetes: the clinical and diagnostic utility of a gene panel-based next-generation sequencing approach. Mol Genet Metab. 2014;113(4):315-320
24. Greeley SA, John PM, Winn AN, et al. The cost-effectiveness of personalized genetic medicine: the case of genetic testing in neonatal diabetes. Diabetes Care. 2011;34(3):622-627
25. Naylor RN, John PM, Winn AN, et al. Cost-effectiveness of MODY genetic testing: translating genomic advances into practical health applications. Diabetes Care. 2014;37(1):202-209
26. De Franco E, Flanagan SE, Houghton JA, et al. The effect of early, comprehensive genomic testing on clinical care in neonatal diabetes: an international cohort study. Lancet. 2015;386(9997):957-963
27. Iafusco D, Stazi MA, Cotichini R, et al. Permanent diabetes mellitus in the first year of life. Diabetologia. 2002;45(6):798-804
28. Ellard S, Bellanne-Chantelot C, Hattersley AT. Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young. Diabetologia. 2008;51(4):546-553
29. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-424
30. Edghill EL, Dix RJ, Flanagan SE, et al. HLA genotyping supports a nonautoimmune etiology in patients diagnosed with diabetes under the age of 6 months. Diabetes. 2006;55(6):1895-1898
31. Rubio-Cabezas O, Minton JA, Caswell R, et al. Clinical heterogeneity in patients with FOXP3 mutations presenting with permanent neonatal diabetes. Diabetes Care. 2009;32(1):111-116
32. Flanagan SE, Haapaniemi E, Russell MA, et al. Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease. Nat Genet. 2014;46(8):812-814
33. Johnson MB, De Franco E, Lango Allen H, et al. Recessively inherited LRBA mutations cause autoimmunity presenting as neonatal diabetes. Diabetes. 2017;66(8):2316-2322
34. Rubio-Cabezas O, Flanagan SE, Damhuis A, Hattersley AT, Ellard S. KATP channel mutations in infants with permanent diabetes diagnosed after 6 months of life. Pediatr Diabetes. 2012;13(4):322-325
35. Mohamadi A, Clark LM, Lipkin PH, Mahone EM, Wodka EL, Plotnick LP. Medical and developmental impact of transition from subcutaneous insulin to oral glyburide in a 15-yr-old boy with neonatal diabetes mellitus and intermediate DEND syndrome: extending the age of KCNJ11 mutation testing in neonatal DM. Pediatr Diabetes. 2010;11(3):203-207
36. Temple IK, Gardner RJ, Mackay DJ, Barber JC, Robinson DO, Shield JP. Transient neonatal diabetes: widening the understanding of the etiopathogenesis of diabetes. Diabetes. 2000;49(8):1359-1366
37. Gardner RJ, Mackay DJ, Mungall AJ, et al. An imprinted locus associated with transient neonatal diabetes mellitus. Hum Mol Genet. 2000;9(4):589-596
38. 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(7):1930-1937
39. Yorifuji T, Kurokawa K, Mamada M, et al. Neonatal diabetes mellitus and neonatal polycystic, dysplastic kidneys: phenotypically discordant recurrence of a mutation in the hepatocyte nuclear factor-1beta gene due to germline mosaicism. J Clin Endocrinol Metabol. 2004;89(6):2905-2908
40. Garin I, Edghill EL, Akerman I, et al. Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis. Proc Natl Acad Sci U S A. 2010;107(7):3105-3110
41. Russo L, Iafusco D, Brescianini S, et al. Permanent diabetes during the first year of life: multiple gene screening in 54 patients. Diabetologia. 2011;54(7):1693-1701
42. Rubio-Cabezas O, Ellard S. Diabetes mellitus in neonates and infants: genetic heterogeneity, clinical approach to diagnosis, and therapeutic options. Horm Res Paediatr. 2013;80(3):137-146
43. Mackay D, Bens S, Perez de Nanclares G, Siebert R, Temple IK. Clinical utility gene card for: transient neonatal diabetes mellitus, 6q24-related. Eur J Hum Genet. 2014;22(9). https://doi.org/10.1038/ejhg.2014.27
44. Ma D, Shield JP, Dean W, et al. Impaired glucose homeostasis in transgenic mice expressing the human transient neonatal diabetes mellitus locus, TNDM. J Clin Invest. 2004;114(3):339-348
45. Temple IK, Shield JP. Transient neonatal diabetes, a disorder of imprinting. J Med Genet. 2002;39(12):872-875
46. Mackay DJ, Boonen SE, Clayton-Smith J, et al. A maternal hypomethylation syndrome presenting as transient neonatal diabetes mellitus. Hum Genet. 2006;120(2):262-269
47. 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(8):949-951
48. Docherty LE, Kabwama S, Lehmann A, et al. Clinical presentation of 6q24 transient neonatal diabetes mellitus (6q24 TNDM) and genotype-phenotype correlation in an international cohort of patients. Diabetologia. 2013;56(4):758-762
49. Flanagan SE, Mackay DJ, Greeley SA, et al. Hypoglycaemia following diabetes remission in patients with 6q24 methylation defects: expanding the clinical phenotype. Diabetologia. 2013;56(1):218-221
50. Kalaivanan P, Arya VB, Shah P, et al. Chromosome 6q24 transient neonatal diabetes mellitus and protein sensitive hyperinsulinaemic hypoglycaemia. J Pediatr Endocrinol Metab. 2014;27(11–12):1065-1069
51. 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(4):F341-F343
52. Busiah K, Drunat S, Vaivre-Douret L, et al. Neuropsychological dysfunction and developmental defects associated with genetic changes in infants with neonatal diabetes mellitus: a prospective cohort study [corrected]. Lancet Diabetes Endocrinol. 2013;1(3):199-207
53. Sovik O, Aagenaes O, Eide SA, et al. Familial occurrence of neonatal diabetes with duplications in chromosome 6q24: treatment with sulfonylurea and 40-yr follow-up. Pediatr Diabetes. 2012;13(2):155-162
54. Yorifuji T, Hashimoto Y, Kawakita R, et al. Relapsing 6q24-related transient neonatal diabetes mellitus successfully treated with a dipeptidyl peptidase-4 inhibitor: a case report. Pediatr Diabetes. 2014;15(8):606-610
55. Carmody D, Beca FA, Bell CD, et al. Role of noninsulin therapies alone or in combination in chromosome 6q24-related transient neonatal diabetes: sulfonylurea improves but does not always normalize insulin secretion. Diabetes Care. 2015;38(6):e86-e87
56. Yorifuji T, Matsubara K, Sakakibara A, et al. Abnormalities in chromosome 6q24 as a cause of early-onset, non-obese, non-autoimmune diabetes mellitus without history of neonatal diabetes. Diabet Med. 2015;32(7):963-967
57. 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(Pt 17):3201-3209
58. Ashcroft FM. ATP-sensitive potassium channelopathies: focus on insulin secretion. J Clin Invest. 2005;115(8):2047-2058
59. Babenko AP, Polak M, Cavé H, et al. Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. N Engl J Med. 2006;355(5):456-466
60. Ellard S, Flanagan SE, Girard CA, et al. Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects. Am J Hum Genet. 2007;81(2):375-382
61. Flanagan SE, Edghill EL, Gloyn AL, Ellard S, Hattersley AT. 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
62. 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(10):2719-2722
63. Flanagan SE, Dung VC, Houghton JAL, et al. An ABCC8 nonsense mutation causing neonatal diabetes through altered transcript expression. J Clin Res Pediatr Endocrinol. 2017;9(3):260-264
64. Proks P, Arnold AL, Bruining J, et al. A heterozygous activating mutation in the sulphonylurea receptor SUR1 (ABCC8) causes neonatal diabetes. Hum Mol Genet. 2006;15(11):1793-1800
65. Letourneau LR, Carmody D, Wroblewski K, et al. Diabetes presentation in infancy: high risk of diabetic ketoacidosis. Diabetes Care. 2017;40(10):e147-e148
66. 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. 2006;14(7):824-830
67. Hattersley AT, 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
68. Clark RH, McTaggart JS, Webster R, et al. Muscle dysfunction caused by a KATP channel mutation in neonatal diabetes is neuronal in origin. Science. 2010;329(5990):458-461
69. Beltrand J, Elie C, Busiah K, et al. Sulfonylurea therapy benefits neurological and psychomotor functions in patients with neonatal diabetes owing to potassium channel mutations. Diabetes Care. 2015;38(11):2033-2041
70. Carmody D, Pastore AN, Landmeier KA, et al. Patients with KCNJ11-related diabetes frequently have neuropsychological impairments compared with sibling controls. Diabet Med. 2016;33(10):1380-1386
71. Bowman P, Broadbridge E, Knight BA, et al. Psychiatric morbidity in children with KCNJ11 neonatal diabetes. Diabet Med. 2016;33(10):1387-1391
72. Landmeier KA, Lanning M, Carmody D, Greeley SAW, Msall ME. ADHD, learning difficulties and sleep disturbances associated with KCNJ11-related neonatal diabetes. Pediatr Diabetes. 2017;18(7):518-523
73. Pearson ER, Flechtner I, Njølstad PR, et al. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N Engl J Med. 2006;355(5):467-477
74. Rafiq M, Flanagan SE, Patch AM, et al. Effective treatment with oral sulfonylureas in patients with diabetes due to sulfonylurea receptor 1 (SUR1) mutations. Diabetes Care. 2008;31(2):204-209
75. European Medicines Agency Assessment Report EMA/123611/2018, European Medicines Agency, 2018. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/004379/WC500250428.pdf (accessed on July 8 2018)
76. Bowman P, Sulen A, Barbetti F, et al. Effectiveness and safety of long-term treatment with sulfonylureas in patients with neonatal diabetes due to KCNJ11 mutations: an international cohort study. Lancet Diabetes Endocrinol. 2018;6:637-646
77. Lanning MS, Carmody D, Szczerbinski L, Letourneau LR, Naylor RN, SAW G. Hypoglycemia in sulfonylurea-treated KCNJ11-neonatal diabetes: mild-moderate symptomatic episodes occur infrequently but none involving unconsciousness or seizures. Pediatr Diabetes. 2018;19(3):393-397
78. 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(10):2713-2718
79. Greeley SA, Tucker SE, Naylor RN, Bell GI, Philipson LH. Neonatal diabetes mellitus: a model for personalized medicine. Trends Endocrinol Metab. 2010;21(8):464-472
80. Thurber BW, Carmody D, Tadie EC, et al. Age at the time of sulfonylurea initiation influences treatment outcomes in KCNJ11-related neonatal diabetes. Diabetologia. 2015;58(7):1430-1435
81. Babiker T, Vedovato N, Patel K, et al. Successful transfer to sulfonylureas in KCNJ11 neonatal diabetes is determined by the mutation and duration of diabetes. Diabetologia. 2016;59(6):1162-1166
82. Klupa T, Skupien J, Mirkiewicz-Sieradzka B, et al. Efficacy and safety of sulfonylurea use in permanent neonatal diabetes due to KCNJ11 gene mutations: 34-month median follow-up. Diabetes Technol Ther. 2010;12(5):387-391
83. Codner E, Flanagan S, Ellard S, García H, Hattersley AT. High-dose glibenclamide can replace insulin therapy despite transitory diarrhea in early-onset diabetes caused by a novel R201L Kir6.2 mutation. Diabetes Care. 2005;28(3):758-759
84. Kumaraguru J, Flanagan SE, Greeley SA, et al. Tooth discoloration in patients with neonatal diabetes after transfer onto glibenclamide: a previously unreported side effect. Diabetes Care. 2009;32(8):1428-1430
85. 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(11):640-645
86. Fendler W, Pietrzak I, Brereton MF, et al. Switching to sulphonylureas in children with iDEND syndrome caused by KCNJ11 mutations results in improved cerebellar perfusion. Diabetes Care. 2013;36(8):2311-2316
87. Lahmann C, Kramer HB, Ashcroft FM. Systemic administration of glibenclamide fails to achieve therapeutic levels in the brain and cerebrospinal fluid of rodents. PLoS One. 2015;10(7):e0134476
88. Battaglia D, Lin YW, Brogna C, et al. Glyburide ameliorates motor coordination and glucose homeostasis in a child with diabetes associated with the KCNJ11/S225T, del226-232 mutation. Pediatr Diabetes. 2012;13(8):656-660
89. Gurgel LC, Crispim F, Noffs MH, Belzunces E, Rahal MA, Moisés RS. Sulfonylrea treatment in permanent neonatal diabetes due to G53D mutation in the KCNJ11 gene: improvement in glycemic control and neurological function. Diabetes Care. 2007;30(11):e108
90. Koster JC, Cadario F, Peruzzi C, Colombo C, Nichols CG, Barbetti F. 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(3):1054-1061
91. Shah RP, Spruyt K, Kragie BC, Greeley SA, Msall ME. Visuomotor performance in KCNJ11-related neonatal diabetes is impaired in children with DEND-associated mutations and may be improved by early treatment with sulfonylureas. Diabetes Care. 2012;35(10):2086-2088
92. Edghill EL, Gloyn AL, Goriely A, et al. Origin of de novo KCNJ11 mutations and risk of neonatal diabetes for subsequent siblings. J Clin Endocrinol Metab. 2007;92(5):1773-1777
93. 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
94. Polak M, Dechaume A, Cave H, et al. Heterozygous missense mutations in the insulin gene are linked to permanent diabetes appearing in the neonatal period or in early infancy: a report from the French ND (neonatal diabetes) study group. Diabetes. 2008;57(4):1115-1119
95. Molven A, Ringdal M, Nordbo AM, et al. Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes. Diabetes. 2008;57(4):1131-1135
96. Delépine M, Nicolino M, Barrett T, Golamaully M, Lathrop GM, Julier C. EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome. Nat Genet. 2000;25(4):406-409
97. Senée V, Vattem KM, Delépine M, et al. Wolcott-Rallison syndrome: clinical, genetic, and functional study of EIF2AK3 mutations and suggestion of genetic heterogeneity. Diabetes. 2004;53(7):1876-1883
98. Habeb AM, Flanagan SE, Deeb A, et al. Permanent neonatal diabetes: different aetiology in Arabs compared to Europeans. Arch Dis Child. 2012;97(8):721-723
99. Rubio-Cabezas O, Patch AM, Minton JA, et al. Wolcott-Rallison syndrome is the most common genetic cause of permanent neonatal diabetes in consanguineous families. J Clin Endocrinol Metabol. 2009;94(11):4162-4170
100. Matschinsky FM. Glucokinase, glucose homeostasis, and diabetes mellitus. Curr Diab Rep. 2005;5(3):171-176
101. Njolstad PR, Sagen JV, Bjorkhaug L, et al. Permanent neonatal diabetes caused by glucokinase deficiency: inborn error of the glucose-insulin signaling pathway. Diabetes. 2003;52(11):2854-2860
102. Njølstad PR, Søvik O, Cuesta-Muñoz A, et al. Neonatal diabetes mellitus due to complete glucokinase deficiency. N Engl J Med. 2001;344(21):1588-1592
103. Bennett CL, Christie J, Ramsdell F, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet. 2001;27(1):20-21
104. Verbsky JW, Chatila TA. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) and IPEX-related disorders: an evolving web of heritable autoimmune diseases. Curr Opin Pediatr. 2013;25(6):708-714
105. Bindl L, Torgerson T, Perroni L, et al. Successful use of the new immune-suppressor sirolimus in IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome). J Pediatr. 2005;147(2):256-259
106. Yong PL, Russo P, Sullivan KE. Use of sirolimus in IPEX and IPEX-like children. J Clin Immunol. 2008;28(5):581-587
107. Rao A, Kamani N, Filipovich A, et al. Successful bone marrow transplantation for IPEX syndrome after reduced-intensity conditioning. Blood. 2007;109(1):383-385
108. Weedon MN, Cebola I, Patch AM, et al. Recessive mutations in a distal PTF1A enhancer cause isolated pancreatic agenesis. Nat Genet. 2014;46(1):61-64
109. Lango Allen H, Flanagan SE, Shaw-Smith C, et al. GATA6 haploinsufficiency causes pancreatic agenesis in humans. Nat Genet. 2012;44(1):20-22
110. Habeb AM, Flanagan SE, Zulali MA, et al. Pharmacogenomics in diabetes: outcomes of thiamine therapy in TRMA syndrome. Diabetologia. 2018;61(5):1027-1036
111. Besser RE, Flanagan SE, Mackay DG, Temple IK, Shepherd MH, Shields BM, Ellard S, Hattersley AT. Prematurity and Genetic Testing for Neonatal Diabete. Hattersley AT. Pediatrics. 2016;138(3) pii: e20153926. https://doi.org/10.1542/peds.2015-3926
112. American DA. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S13-S27
113. Shields BM, Hicks S, Shepherd MH, Colclough K, Hattersley AT, Ellard S. Maturity-onset diabetes of the young (MODY): how many cases are we missing? Diabetologia. 2010;53(12):2504-2508
114. Stanik J, Dusatkova P, Cinek O, et al. De novo mutations of GCK, HNF1A and HNF4A may be more frequent in MODY than previously assumed. Diabetologia. 2014;57(3):480-484
115. 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(1):54-62
116. Lorini R, Alibrandi A, Vitali L, et al. Risk of type 1 diabetes development in children with incidental hyperglycemia: a multicenter Italian study. Diabetes Care. 2001;24(7):1210-1216
117. Lorini R, Klersy C, d'Annunzio G, et al. Maturity-onset diabetes of the young in children with incidental hyperglycemia: a multicenter Italian study of 172 families. Diabetes Care. 2009;32(10):1864-1866
118. Prisco F, Iafusco D, Franzese A, Sulli N, Barbetti F. MODY 2 presenting as neonatal hyperglycaemia: a need to reshape the definition of "neonatal diabetes"? Diabetologia. 2000;43(10):1331-1332
119. Steele AM, Wensley KJ, Ellard S, et al. Use of HbA1c in the identification of patients with hyperglycaemia caused by a glucokinase mutation: observational case control studies. PLoS One. 2013;8(6):e65326
120. Stride A, Vaxillaire M, Tuomi T, et al. The genetic abnormality in the beta cell determines the response to an oral glucose load. Diabetologia. 2002;45(3):427-435
121. Chakera AJ, Spyer G, Vincent N, Ellard S, Hattersley AT, Dunne FP. The 0.1% of the population with glucokinase monogenic diabetes can be recognized by clinical characteristics in pregnancy: the Atlantic Diabetes in Pregnancy cohort. Diabetes Care. 2014;37(5):1230-1236
122. Rudland VL, Hinchcliffe M, Pinner J, et al. Identifying glucokinase monogenic diabetes in a multiethnic gestational diabetes mellitus cohort: new pregnancy screening criteria and utility of HbA1c. Diabetes Care. 2016;39(1):50-52
123. Steele AM, Shields BM, Wensley KJ, Colclough K, Ellard S, Hattersley AT. Prevalence of vascular complications among patients with glucokinase mutations and prolonged, mild hyperglycemia. JAMA. 2014;311(3):279-286
124. Velho G, Blanché H, Vaxillaire M, et al. Identification of 14 new glucokinase mutations and description of the clinical profile of 42 MODY-2 families. Diabetologia. 1997;40(2):217-224
125. Stride A, Shields B, Gill-Carey O, et al. Cross-sectional and longitudinal studies suggest pharmacological treatment used in patients with glucokinase mutations does not alter glycaemia. Diabetologia. 2014;57(1):54-56
126. Chakera AJ, Steele AM, Gloyn AL, et al. Recognition and management of individuals with hyperglycemia because of a heterozygous glucokinase mutation. Diabetes Care. 2015;38(7):1383-1392
127. Fendler W, Malachowska B, Baranowska-Jazwiecka A, et al. Population-based estimates for double diabetes amongst people with glucokinase monogenic diabetes, GCK-MODY. Diabet Med. 2014;31(7):881-883
128. 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(5):878-885
129. Ostoft SH, Bagger JI, Hansen T, et al. Incretin effect and glucagon responses to oral and intravenous glucose in patients with maturity onset diabetes of the young—type 2 and type 3. Diabetes. 2014;63:2838-2844
130. Isomaa B, Henricsson M, Lehto M, et al. Chronic diabetic complications in patients with MODY3 diabetes. Diabetologia. 1998;41(4):467-473
131. Steele AM, Shields BM, Shepherd M, Ellard S, Hattersley AT, Pearson ER. Increased all-cause and cardiovascular mortality in monogenic diabetes as a result of mutations in the HNF1A gene. Diabet Med. 2010;27(2):157-161
132. Bellanne-Chantelot C, Carette C, Riveline JP, et al. The type and the position of HNF1A mutation modulate age at diagnosis of diabetes in patients with maturity-onset diabetes of the young (MODY)-3. Diabetes. 2008;57(2):503-508
133. Harries LW, Ellard S, Stride A, Morgan NG, Hattersley AT. Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1 alpha show differential expression in the pancreas and define the relationship between mutation position and clinical phenotype in monogenic diabetes. Hum Mol Genet. 2006;15(14):2216-2224
134. Stride A, Ellard S, Clark P, et al. Beta-cell dysfunction, insulin sensitivity, and glycosuria precede diabetes in hepatocyte nuclear factor-1alpha mutation carriers. Diabetes Care. 2005;28(7):1751-1756
135. Hamilton AJ, Bingham C, McDonald TJ, et al. The HNF4A R76W mutation causes atypical dominant Fanconi syndrome in addition to a beta cell phenotype. J Med Genet. 2014;51(3):165-169
136. 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(4):e118
137. Flanagan SE, Kapoor RR, Mali G, et al. Diazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations. Eur J Endocrinol. 2010;162(5):987-992
138. Kapoor RR, Locke J, Colclough K, et al. Persistent hyperinsulinemic hypoglycemia and maturity-onset diabetes of the young due to heterozygous HNF4A mutations. Diabetes. 2008;57(6):1659-1663
139. Stanescu DE, Hughes N, Kaplan B, Stanley CA, De Leon DD. Novel presentations of congenital hyperinsulinism due to mutations in the MODY genes: HNF1A and HNF4A. J Clin Endocrinol Metab. 2012;97(10):E2026-E2030
140. Pearson ER, Starkey BJ, Powell RJ, Gribble FM, Clark PM, Hattersley AT. Genetic cause of hyperglycaemia and response to treatment in diabetes. Lancet. 2003;362(9392):1275-1281
141. Byrne MM, Sturis J, Menzel S, et al. Altered insulin secretory responses to glucose in diabetic and nondiabetic subjects with mutations in the diabetes susceptibility gene MODY3 on chromosome 12. Diabetes. 1996;45(11):1503-1510
142. Fajans SS, Brown MB. Administration of sulfonylureas can increase glucose-induced insulin secretion for decades in patients with maturity-onset diabetes of the young. Diabetes Care. 1993;16(9):1254-1261
143. Shepherd M, Shields B, Ellard S, Rubio-Cabezas O, Hattersley AT. A genetic diagnosis of HNF1A diabetes alters treatment and improves glycaemic control in the majority of insulin-treated patients. Diabet Med. 2009;26(4):437-441
144. Raile K, Schober E, Konrad K, et al. Treatment of young patients with HNF1A mutations (HNF1A-MODY). Diabet Med. 2015;32(4):526-530
145. Ostoft SH, Bagger JI, Hansen T, et al. Glucose-lowering effects and low risk of hypoglycemia in patients with maturity-onset diabetes of the young when treated with a GLP-1 receptor agonist: a double-blind, randomized, crossover trial. Diabetes Care. 2014;37(7):1797-805
146. Schmidt F, Kapellen TM, Wiegand S, et al. Diabetes mellitus in children and adolescents with genetic syndromes. Exp Clin Endocrinol Diabetes. 2012;120(10):579-585
147. Farmer A, Ayme S, de Heredia ML, et al. EURO-WABB: an EU rare diseases registry for Wolfram syndrome, Alstrom syndrome and Bardet-Biedl syndrome. BMC Pediatr. 2013;13:130
148. Inoue H, Tanizawa Y, Wasson J, et al. A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). Nat Genet. 1998;20(2):143-148
149. Barrett TG, Bundey SE, Macleod AF. Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome. Lancet. 1995;346(8988):1458-1463
150. Marshall BA, Permutt MA, Paciorkowski AR, et al. Phenotypic characteristics of early Wolfram syndrome. Orphanet J Rare Dis. 2013;8:64
151. Karzon R, Narayanan A, Chen L, Lieu JEC, Hershey T. Longitudinal hearing loss in Wolfram syndrome. Orphanet J Rare Dis. 2018;13(1):102
152. Bueno GE, Ruiz-Castaneda D, Martinez JR, Munoz MR, Alascio PC. Natural history and clinical characteristics of 50 patients with Wolfram syndrome. Endocrine. 2018;61:440-446
153. de Heredia ML, Cleries R, Nunes V. Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype. Genet Med. 2013;15(7):497-506
154. Zmyslowska A, Borowiec M, Fichna P, et al. Delayed recognition of Wolfram syndrome frequently misdiagnosed as type 1 diabetes with early chronic complications. Exp Clin Endocrinol Diabetes. 2014;122(1):35-38
155. Khanim F, Kirk J, Latif F, Barrett TG. WFS1/wolframin mutations, Wolfram syndrome, and associated diseases. Hum Mutat. 2001;17(5):357-367
156. Amr S, Heisey C, Zhang M, et al. A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. Am J Hum Genet. 2007;81(4):673-683
157. Bingham C, Hattersley AT. Renal cysts and diabetes syndrome resulting from mutations in hepatocyte nuclear factor-1beta. Nephrol Dial Transplant. 2004;19(11):2703-2708
158. Ulinski T, Lescure S, Beaufils S, et al. Renal phenotypes related to hepatocyte nuclear factor-1beta (TCF2) mutations in a pediatric cohort. J Am Soc Nephrol. 2006;17(2):497-503
159. Edghill EL, Bingham C, Ellard S, Hattersley AT. Mutations in hepatocyte nuclear factor-1beta and their related phenotypes. J Med Genet. 2006;43(1):84-90
160. Raile K, Klopocki E, Holder M, et al. Expanded clinical spectrum in hepatocyte nuclear factor 1b-maturity-onset diabetes of the young. J Clin Endocrinol Metab. 2009;94(7):2658-2664
161. Edghill EL, Bingham C, Slingerland AS, et al. Hepatocyte nuclear factor-1 beta mutations cause neonatal diabetes and intrauterine growth retardation: support for a critical role of HNF-1beta in human pancreatic development. Diabet Med. 2006;23(12):1301-1306
162. Bellanné-Chantelot C, Chauveau D, Gautier JF, et al. Clinical spectrum associated with hepatocyte nuclear factor-1beta mutations. Ann Intern Med. 2004;140(7):510-517
163. Pearson ER, Badman MK, Lockwood CR, et al. Contrasting diabetes phenotypes associated with hepatocyte nuclear factor-1alpha and -1beta mutations. Diabetes Care. 2004;27(5):1102-1107
164. Tjora E, Wathle G, Erchinger F, et al. Exocrine pancreatic function in hepatocyte nuclear factor 1beta-maturity-onset diabetes of the young (HNF1B-MODY) is only moderately reduced: compensatory hypersecretion from a hypoplastic pancreas. Diabet Med. 2013;30(8):946-955
165. Haldorsen IS, Vesterhus M, Raeder H, et al. Lack of pancreatic body and tail in HNF1B mutation carriers. Diabet Med. 2008;25(7):782-787
166. Reinauer C, Meissner T, Roden M, et al. Low prevalence of patients with mitochondrial disease in the German/Austrian DPV diabetes registry. Eur J Pediatr. 2016;175(5):613-622
167. Maassen JA, LM TH, Van Essen E, et al. Mitochondrial diabetes: molecular mechanisms and clinical presentation. Diabetes. 2004;53(Suppl 1):S103-S109
168. Guillausseau PJ, Dubois-Laforgue D, Massin P, et al. Heterogeneity of diabetes phenotype in patients with 3243 bp mutation of mitochondrial DNA (Maternally Inherited Diabetes and Deafness or MIDD). Diabetes Metab. 2004;30(2):181-186
169. Laloi-Michelin M, Meas T, Ambonville C, et al. 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(8):3025-3030
170. Goto Y, Nonaka I, Horai S. A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature. 1990;348(6302):651-653
171. Lalau JD. Lactic acidosis induced by metformin: incidence, management and prevention. Drug Saf. 2010;33(9):727-740
172. Laloi-Michelin M, Virally M, Jardel C, et al. Kearns Sayre syndrome: an unusual form of mitochondrial diabetes. Diabetes Metab. 2006;32(2):182-186
173. Superti-Furga A, Schoenle E, Tuchschmid P, et al. Pearson bone marrow-pancreas syndrome with insulin-dependent diabetes, progressive renal tubulopathy, organic aciduria and elevated fetal haemoglobin caused by deletion and duplication of mitochondrial DNA. Eur J Pediatr. 1993;152(1):44-50
174. Raeder H, Haldorsen IS, Ersland L, et al. Pancreatic lipomatosis is a structural marker in nondiabetic children with mutations in carboxyl-ester lipase. Diabetes. 2007;56(2):444-449
175. Raeder H, McAllister FE, Tjora E, et al. Carboxyl-ester lipase maturity-onset diabetes of the young is associated with development of pancreatic cysts and upregulated MAPK signaling in secretin-stimulated duodenal fluid. Diabetes. 2014;63(1):259-269
176. Rebours V, Boutron-Ruault MC, Schnee M, et al. The natural history of hereditary pancreatitis: a national series. Gut. 2009;58(1):97-103
177. Semple RK, Savage DB, Cochran EK, Gorden P, O'Rahilly S. Genetic syndromes of severe insulin resistance. Endocr Rev. 2011;32(4):498-514
178. Parker VE, Semple RK. Genetics in endocrinology: genetic forms of severe insulin resistance: what endocrinologists should know. Eur J Endocrinol. 2013;169(4):R71-R80
179. 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(4):209-222
180. Regan FM, Williams RM, McDonald A, et al. Treatment with recombinant human insulin-like growth factor (rhIGF)-I/rhIGF binding protein-3 complex improves metabolic control in subjects with severe insulin resistance. J Clin Endocrinol Metab. 2010;95(5):2113-2122
181. Carmody D, Ladsaria SS, Buikema RK, Semple RK, Greeley SA. Successful rhIGF1 treatment for over 5 years in a patient with severe insulin resistance due to homozygous insulin receptor mutation. Diabet Med. 2016;33(3):e8-e12
182. Garg A. Acquired and inherited lipodystrophies. N Engl J Med. 2004;350(12):1220-1234
183. Brown RJ, Araujo-Vilar D, Cheung PT, et al. The diagnosis and management of lipodystrophy syndromes: a multi-society practice guideline. J Clin Endocrinol Metab. 2016;101(12):4500-4511
184. Agarwal AK, Simha V, Oral EA, et al. Phenotypic and genetic heterogeneity in congenital generalized lipodystrophy. J Clin Endocrinol Metab. 2003;88(10):4840-4847
185. Weedon MN, Ellard S, Prindle MJ, et al. An in-frame deletion at the polymerase active site of POLD1 causes a multisystem disorder with lipodystrophy. Nat Genet. 2013;45(8):947-950
186. Chudasama KK, Winnay J, Johansson S, et al. SHORT syndrome with partial lipodystrophy due to impaired phosphatidylinositol 3 kinase signaling. Am J Hum Genet. 2013;93(1):150-157
187. Owen KR, Donohoe M, Ellard S, Hattersley AT. Response to treatment with rosiglitazone in familial partial lipodystrophy due to a mutation in the LMNA gene. Diabet Med. 2003;20(10):823-827
188. Brown RJ, Oral EA, Cochran E, et al. Long-term effectiveness and safety of metreleptin in the treatment of patients with generalized lipodystrophy. Endocrine. 2018;60(3):479-489
189. Simha V, Subramanyam L, Szczepaniak L, et al. Comparison of efficacy and safety of leptin replacement therapy in moderately and severely hypoleptinemic patients with familial partial lipodystrophy of the Dunnigan variety. J Clin Endocrinol Metab. 2012;97(3):785-792
190. Alstrom CH, Hallgren B, Nilsson LB, Asander H. Retinal degeneration combined with obesity, diabetes mellitus and neurogenous deafness: a specific syndrome (not hitherto described) distinct from the Laurence-Moon-Bardet-Biedl syndrome: a clinical, endocrinological and genetic examination based on a large pedigree. Acta Psychiatr Neurol Scand Suppl. 1959;129:1-35
191. Hearn T, Renforth GL, Spalluto C, et al. Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alstrom syndrome. Nat Genet. 2002;31(1):79-83
192. Mokashi A, Cummings EA. Presentation and course of diabetes in children and adolescents with Alstrom syndrome. Pediatr Diabetes. 2011;12(3 Pt 2):270-275
193. Paisey RB, Geberhiwot T, Waterson M, et al. Modification of severe insulin resistant diabetes in response to lifestyle changes in Alstrom syndrome. Eur J Med Genet. 2014;57(2–3):71-75
194. Tobin JL, Beales PL. Bardet-Biedl syndrome: beyond the cilium. Pediatr Nephrol. 2007;22(7):926-936
195. Scheidecker S, Etard C, Pierce NW, et al. Exome sequencing of Bardet-Biedl syndrome patient identifies a null mutation in the BBSome subunit BBIP1 (BBS18). J Med Genet. 2014;51(2):132-136
196. Guo DF, Rahmouni K. Molecular basis of the obesity associated with Bardet-Biedl syndrome. Trends Endocrinol Metab. 2011;22(7):286-293
197. Abu-Safieh L, Al-Anazi S, Al-Abdi L, et al. In search of triallelism in Bardet-Biedl syndrome. Eur J Hum Genet. 2012;20(4):420-427
198. Katsanis N, Ansley SJ, Badano JL, et al. Triallelic inheritance in Bardet-Biedl syndrome, a Mendelian recessive disorder. Science. 2001;293(5538):2256-2259
199. Edghill EL, Flanagan SE, Ellard S. Permanent neonatal diabetes due to activating mutations in ABCC8 and KCNJ11. Rev Endocr Metab Disord. 2010;11(3):193-198
200. Stoffers DA, Ferrer J, Clarke WL, Habener JF. Early-onset type-II diabetes mellitus (MODY4) linked to IPF1. Nat Genet. 1997;17(2):138-139
201. Sellick GS, Barker KT, Stolte-Dijkstra I, et al. Mutations in PTF1A cause pancreatic and cerebellar agenesis. Nat Genet. 2004;36(12):1301-1305
202. Smith SB, Qu HQ, Taleb N, et al. Rfx6 directs islet formation and insulin production in mice and humans. Nature. 2010;463(7282):775-780
203. D'Amato E, Giacopelli F, Giannattasio A, et al. Genetic investigation in an Italian child with an unusual association of atrial septal defect, attributable to a new familial GATA4 gene mutation, and neonatal diabetes due to pancreatic agenesis. Diabet Med. 2010;27(10):1195-1200
204. 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
205. Rubio-Cabezas O, Jensen JN, Hodgson MI, et al. Permanent neonatal diabetes and enteric anendocrinosis associated with biallelic mutations in NEUROG3. Diabetes. 2011;60(4):1349-1353
206. Rubio-Cabezas O, Minton JA, Kantor I, Williams D, Ellard S, Hattersley AT. Homozygous mutations in NEUROD1 are responsible for a novel syndrome of permanent neonatal diabetes and neurological abnormalities. Diabetes. 2010;59(9):2326-2331
207. Solomon BD, Pineda-Alvarez DE, Balog JZ, et al. Compound heterozygosity for mutations in PAX6 in a patient with complex brain anomaly, neonatal diabetes mellitus, and microophthalmia. Am J Med Genet A. 2009;149A(11):2543-2546
208. 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(9):2381-2385
209. Shaw-Smith C, Flanagan SE, Patch AM, et al. Recessive SLC19A2 mutations are a cause of neonatal diabetes mellitus in thiamine-responsive megaloblastic anaemia. Pediatr Diabetes. 2012;13(4):314-321
210. Abdel-Salam GM, Schaffer AE, Zaki MS, et al. A homozygous IER3IP1 mutation causes microcephaly with simplified gyral pattern, epilepsy, and permanent neonatal diabetes syndrome (MEDS). Am J Med Genet A. 2012;158A(11):2788-2796
211. Petrie JR, Chaturvedi N, Ford I, et al. Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2017;5(8):597-609
212. De Franco E, Flanagan SE, Yagi T, et al. Dominant ER stress-inducing WFS1 mutations underlie a genetic syndrome of neonatal/infancy-onset diabetes, congenital sensorineural deafness, and congenital cataracts. Diabetes. 2017;66(7):2044-2053
213. 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(6608):458-460
214. Vionnet N, Stoffel M, Takeda J, et al. Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus. Nature. 1992;356(6371):721-722
215. 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(6608):455-458
216. Horikawa Y, Iwasaki N, Hara M, et al. Mutation in hepatocyte nuclear factor-1 beta gene (TCF2) associated with MODY. Nat Genet. 1997;17(4):384-385