Monogenic Diabetes: Genetics and Relevance on Diabetes Mellitus Personalized Medicine

Author(s): Madalena Sousa, Jácome Bruges-Armas*

Journal Name: Current Diabetes Reviews

Volume 16 , Issue 8 , 2020


Become EABM
Become Reviewer
Call for Editor

Abstract:

Background: Diabetes mellitus (DM) is a complex disease with significant impression in today's world. Aside from the most common types recognized over the years, such as type 1 diabetes (T1DM) and type 2 diabetes (T2DM), recent studies have emphasized the crucial role of genetics in DM, allowing the distinction of monogenic diabetes.

Methods: Authors did a literature search with the purpose of highlighting and clarifying the subtypes of monogenic diabetes, as well as the accredited genetic entities responsible for such phenotypes.

Results: The following subtypes were included in this literature review: maturity-onset diabetes of the young (MODY), neonatal diabetes mellitus (NDM) and maternally inherited diabetes and deafness (MIDD). So far, 14 subtypes of MODY have been identified, while three subtypes have been identified in NDM - transient, permanent, and syndromic.

Discussion: Despite being estimated to affect approximately 2% of all the T2DM patients in Europe, the exact prevalence of MODY is still unknown, accentuating the need for research focused on biomarkers. Consequently, due to its impact in the course of treatment, follow-up of associated complications, and genetic implications for siblings and offspring of affected individuals, it is imperative to diagnose the monogenic forms of DM accurately.

Conclusion: Currently, advances in the genetics field allowed the recognition of new DM subtypes, which until now, were considered slight variations of the typical forms. Thus, it is imperative to act in the close interaction between genetics and clinical manifestations, to facilitate diagnosis and individualize treatment.

Keywords: Diabetes mellitus, genetics, monogenic diabetes, maturity-onset diabetes of the young, neonatal diabetes, maternally inherited diabetes and deafness.

[1]
Roglic G. World Health Organization Global report on diabetes. Geneva: World Health Organization 2016.
[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(4): 546-53.
[http://dx.doi.org/10.1007/s00125-008-0942-y] [PMID: 18297260]
[3]
Anık A, Çatlı G, Abacı A, Böber E. Maturity-onset diabetes of the young (MODY): an update. J Pediatr Endocrinol Metab 2015; 28(3-4): 251-63.
[http://dx.doi.org/10.1515/jpem-2014-0384] [PMID: 25581748]
[4]
Colclough K, Saint-Martin C, Timsit J, Ellard S, Bellanné-Chantelot C. Clinical utility gene card for: Maturity-onset diabetes of the young. Eur J Hum Genet 2014; 22(9)
[http://dx.doi.org/10.1038/ejhg.2014.14]] [PMID: 24518839]
[5]
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): 427-35.
[http://dx.doi.org/10.1007/s00125-001-0770-9] [PMID: 11914749]
[6]
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): 1751-6.
[http://dx.doi.org/10.2337/diacare.28.7.1751] [PMID: 15983330]
[7]
McDonald TJ, Ellard S. Maturity onset diabetes of the young: identification and diagnosis. Ann Clin Biochem 2013; 50(Pt 5): 403-15.
[http://dx.doi.org/10.1177/0004563213483458] [PMID: 23878349]
[8]
Isomaa B, Henricsson M, Lehto M, et al. Chronic diabetic complications in patients with MODY3 diabetes. Diabetologia 1998; 41(4): 467-73.
[http://dx.doi.org/10.1007/s001250050931] [PMID: 9562352]
[9]
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): 157-61.
[http://dx.doi.org/10.1111/j.1464-5491.2009.02913.x] [PMID: 20546258]
[10]
McDonald TJ, McEneny J, Pearson ER, et al. Lipoprotein composition in HNF1A-MODY: differentiating between HNF1A-MODY and type 2 diabetes. Clin Chim Acta 2012; 413(9-10): 927-32.
[http://dx.doi.org/10.1016/j.cca.2012.02.005] [PMID: 22360925]
[11]
McDonald TJ, Shields BM, Lawry J, et al. High-sensitivity CRP discriminates HNF1A-MODY from other subtypes of diabetes. Diabetes Care 2011; 34(8): 1860-2.
[http://dx.doi.org/10.2337/dc11-0323] [PMID: 21700917]
[12]
Toniatti C, Demartis A, Monaci P, Nicosia A, Ciliberto G. Synergistic trans-activation of the human C-reactive protein promoter by transcription factor HNF-1 binding at two distinct sites. EMBO J 1990; 9(13): 4467-75.
[http://dx.doi.org/10.1002/j.1460-2075.1990.tb07897.x] [PMID: 2265613]
[13]
Reiner AP, Barber MJ, Guan Y, et al. Polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are associated with C-reactive protein. Am J Hum Genet 2008; 82(5): 1193-201.
[http://dx.doi.org/10.1016/j.ajhg.2008.03.017] [PMID: 18439552]
[14]
Ridker PM, Pare G, Parker A, et al. Loci related to metabolic-syndrome pathways including LEPR,HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women’s Genome Health Study. Am J Hum Genet 2008; 82(5): 1185-92.
[http://dx.doi.org/10.1016/j.ajhg.2008.03.015] [PMID: 18439548]
[15]
Colclough K, Bellanne-Chantelot C, Saint-Martin C, Flanagan SE, Ellard S. Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha and 4 alpha in maturity-onset diabetes of the young and hyperinsulinemic hypoglycemia. Hum Mutat 2013; 34(5): 669-85.
[http://dx.doi.org/10.1002/humu.22279] [PMID: 23348805]
[16]
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): 2216-24.
[http://dx.doi.org/10.1093/hmg/ddl147] [PMID: 16760222]
[17]
Mishra R, Chesi A, Cousminer DL, et al. Bone Mineral Density in Childhood Study. Relative contribution of type 1 and type 2 diabetes loci to the genetic etiology of adult-onset, non-insulin-requiring autoimmune diabetes. BMC Med 2017; 15(1): 88.
[http://dx.doi.org/10.1186/s12916-017-0846-0] [PMID: 28438156]
[18]
Estrada K, Aukrust I, Bjørkhaug L, et al. SIGMA Type 2 Diabetes Consortium. Association of a low-frequency variant in HNF1A with type 2 diabetes in a Latino population. JAMA 2014; 311(22): 2305-14.
[http://dx.doi.org/10.1001/jama.2014.6511] [PMID: 24915262]
[19]
Hegele RA, Hanley AJ, Zinman B, Harris SB, Anderson CM. Youth-onset type 2 diabetes (Y2DM) associated with HNF1A S319 in aboriginal Canadians. Diabetes Care 1999; 22(12): 2095-6.
[http://dx.doi.org/10.2337/diacare.22.12.2095] [PMID: 10587858]
[20]
Najmi LA, Aukrust I, Flannick J, et al. functional investigations of HNF1A identify rare variants as risk factors for type 2 diabetes in the general population. Diabetes 2017; 66(2): 335-46.
[http://dx.doi.org/10.2337/db16-0460] [PMID: 27899486]
[21]
Chiu KC, Chuang LM, Ryu JM, Tsai GP, Saad MF. The I27L amino acid polymorphism of hepatic nuclear factor-1alpha is associated with insulin resistance. J Clin Endocrinol Metab 2000; 85(6): 2178-83.
[PMID: 10852449]
[22]
Gaulton KJ, Ferreira T, Lee Y, et al. Diabetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium. Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci. Nat Genet 2015; 47(12): 1415-25.
[http://dx.doi.org/10.1038/ng.3437] [PMID: 26551672]
[23]
Holmkvist J, Cervin C, Lyssenko V, et al. Common variants in HNF-1 alpha and risk of type 2 diabetes. Diabetologia 2006; 49(12): 2882-91.
[http://dx.doi.org/10.1007/s00125-006-0450-x] [PMID: 17033837]
[24]
Baldini SF, Steenackers A, Olivier-Van Stichelen S, et al. Glucokinase expression is regulated by glucose through O-GlcNAc glycosylation. Biochem Biophys Res Commun 2016; 478(2): 942-8.
[http://dx.doi.org/10.1016/j.bbrc.2016.08.056] [PMID: 27520373]
[25]
Iynedjian PB. Molecular physiology of mammalian glucokinase. Cell Mol Life Sci 2009; 66(1): 27-42.
[http://dx.doi.org/10.1007/s00018-008-8322-9] [PMID: 18726182]
[26]
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(11): 1512-26.
[http://dx.doi.org/10.1002/humu.21110] [PMID: 19790256]
[27]
Byrne MM, Sturis J, Clément K, et al. Insulin secretory abnormalities in subjects with hyperglycemia due to glucokinase mutations. J Clin Invest 1994; 93(3): 1120-30.
[http://dx.doi.org/10.1172/JCI117064] [PMID: 8132752]
[28]
Velho G, Petersen KF, Perseghin G, et al. Impaired hepatic glycogen synthesis in glucokinase-deficient (MODY-2) subjects. J Clin Invest 1996; 98(8): 1755-61.
[http://dx.doi.org/10.1172/JCI118974] [PMID: 8878425]
[29]
Liu S, Ammirati MJ, Song X, et al. Insights into mechanism of glucokinase activation: observation of multiple distinct protein conformations. J Biol Chem 2012; 287(17): 13598-610.
[http://dx.doi.org/10.1074/jbc.M111.274126] [PMID: 22298776]
[30]
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): 217-24.
[http://dx.doi.org/10.1007/s001250050666] [PMID: 9049484]
[31]
Martin D, Bellanné-Chantelot C, Deschamps I, Froguel P, Robert JJ, Velho G. 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(7): 1321-3.
[http://dx.doi.org/10.2337/dc07-2017] [PMID: 18411240]
[32]
Schober E, Rami B, Grabert M, et al. DPV-Wiss Initiative of the German Working Group for Paediatric Diabetology and. Phenotypical aspects of maturity-onset diabetes of the young (MODY diabetes) in comparison with Type 2 diabetes mellitus (T2DM) in children and adolescents: experience from a large multicentre database. Diabet Med 2009; 26(5): 466-73.
[http://dx.doi.org/10.1111/j.1464-5491.2009.02720.x] [PMID: 19646184]
[33]
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): 54-6.
[http://dx.doi.org/10.1007/s00125-013-3075-x] [PMID: 24092492]
[34]
Spyer G, Hattersley AT, Sykes JE, Sturley RH, MacLeod KM. Influence of maternal and fetal glucokinase mutations in gestational diabetes. Am J Obstet Gynecol 2001; 185(1): 240-1.
[http://dx.doi.org/10.1067/mob.2001.113127] [PMID: 11483936]
[35]
Thomson KL, Gloyn AL, Colclough K, et al. Identification of 21 novel glucokinase (GCK) mutations in UK and European Caucasians with maturity-onset diabetes of the young (MODY). Hum Mutat 2003; 22(5): 417.
[http://dx.doi.org/10.1002/humu.9186] [PMID: 14517956]
[36]
Barrio R, Bellanné-Chantelot C, Moreno JC, et al. Nine novel mutations in maturity-onset diabetes of the young (MODY) candidate genes in 22 Spanish families. J Clin Endocrinol Metab 2002; 87(6): 2532-9.
[http://dx.doi.org/10.1210/jcem.87.6.8530] [PMID: 12050210]
[37]
Costa A, Bescós M, Velho G, et al. Genetic and clinical characterisation of maturity-onset diabetes of the young in Spanish families. Eur J Endocrinol 2000; 142(4): 380-6.
[http://dx.doi.org/10.1530/eje.0.1420380] [PMID: 10754480]
[38]
Estalella I, Rica I, Perez de Nanclares G, et al. Spanish MODY Group. Mutations in GCK and HNF-1alpha explain the majority of cases with clinical diagnosis of MODY in Spain. Clin Endocrinol (Oxf) 2007; 67(4): 538-46.
[PMID: 17573900]
[39]
Froguel P, Zouali H, Vionnet N, et al. Familial hyperglycemia due to mutations in glucokinase. Definition of a subtype of diabetes mellitus. N Engl J Med 1993; 328(10): 697-702.
[http://dx.doi.org/10.1056/NEJM199303113281005] [PMID: 8433729]
[40]
Johansen A, Ek J, Mortensen HB, Pedersen O, Hansen T. Half of clinically defined maturity-onset diabetes of the young patients in Denmark do not have mutations in HNF4A, GCK, and TCF1. J Clin Endocrinol Metab 2005; 90(8): 4607-14.
[http://dx.doi.org/10.1210/jc.2005-0196] [PMID: 15928245]
[41]
Mantovani V, Salardi S, Cerreta V, et al. Identification of eight novel glucokinase mutations in Italian children with maturity-onset diabetes of the young. Hum Mutat 2003; 22(4): 338.
[http://dx.doi.org/10.1002/humu.9179] [PMID: 12955723]
[42]
Pruhova S, Ek J, Lebl J, et al. Genetic epidemiology of MODY in the Czech republic: new mutations in the MODY genes HNF-4alpha, GCK and HNF-1alpha. Diabetologia 2003; 46(2): 291-5.
[http://dx.doi.org/10.1007/s00125-002-1010-7] [PMID: 12627330]
[43]
Sagen JV, Bjørkhaug L, Molnes J, et al. Diagnostic screening of MODY2/GCK mutations in the Norwegian MODY Registry. Pediatr Diabetes 2008; 9(5): 442-9.
[http://dx.doi.org/10.1111/j.1399-5448.2008.00399.x] [PMID: 18399931]
[44]
Lehto M, Bitzén PO, Isomaa B, et al. Mutation in the HNF-4alpha gene affects insulin secretion and triglyceride metabolism. Diabetes 1999; 48(2): 423-5.
[http://dx.doi.org/10.2337/diabetes.48.2.423] [PMID: 10334325]
[45]
Laver TW, Colclough K, Shepherd M, et al. The common p.R114W HNF4A mutation causes a distinct clinical subtype of monogenic diabetes. Diabetes 2016; 65(10): 3212-7.
[http://dx.doi.org/10.2337/db16-0628] [PMID: 27486234]
[46]
Wright NM, Metzger DL, Borowitz SM, Clarke WL. Permanent neonatal diabetes mellitus and pancreatic exocrine insufficiency resulting from congenital pancreatic agenesis. Am J Dis Child 1993; 147(6): 607-9.
[PMID: 8506821]
[47]
Stoffers DA, Ferrer J, Clarke WL, Habener JF. Early-onset type-II diabetes mellitus (MODY4) linked to IPF1. Nat Genet 1997; 17(2): 138-9.
[http://dx.doi.org/10.1038/ng1097-138] [PMID: 9326926]
[48]
Fajans SS, Bell GI, Paz VP, et al. Obesity and hyperinsulinemia in a family with pancreatic agenesis and MODY caused by the IPF1 mutation Pro63fsX60. Transl Res 2010; 156(1): 7-14.
[http://dx.doi.org/10.1016/j.trsl.2010.03.003] [PMID: 20621032]
[49]
Thomas IH, Saini NK, Adhikari A, et al. Neonatal diabetes mellitus with pancreatic agenesis in an infant with homozygous IPF-1 Pro63fsX60 mutation. Pediatr Diabetes 2009; 10(7): 492-6.
[http://dx.doi.org/10.1111/j.1399-5448.2009.00526.x] [PMID: 19496967]
[50]
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(3): 323-8.
[http://dx.doi.org/10.1038/15500] [PMID: 10545951]
[51]
Sagen JV, Baumann ME, Salvesen HB, Molven A, Søvik O, Njølstad PR. Diagnostic screening of NEUROD1 (MODY6) in subjects with MODY or gestational diabetes mellitus. Diabet Med 2005; 22(8): 1012-5.
[http://dx.doi.org/10.1111/j.1464-5491.2005.01565.x] [PMID: 16026366]
[52]
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(13): 4807-12.
[http://dx.doi.org/10.1073/pnas.0409177102] [PMID: 15774581]
[53]
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.
[http://dx.doi.org/10.1038/ng1708] [PMID: 16369531]
[54]
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(1): 55-64.
[http://dx.doi.org/10.1007/s00439-009-0740-8] [PMID: 19760265]
[55]
Plengvidhya N, Boonyasrisawat W, Chongjaroen N, et al. Mutations of maturity-onset diabetes of the young (MODY) genes in Thais with early-onset type 2 diabetes mellitus. Clin Endocrinol (Oxf) 2009; 70(6): 847-53.
[http://dx.doi.org/10.1111/j.1365-2265.2008.03397.x] [PMID: 18811724]
[56]
Jo W, Endo M, Ishizu K, Nakamura A, Tajima T. A novel PAX4 mutation in a Japanese patient with maturity-onset diabetes of the young. Tohoku J Exp Med 2011; 223(2): 113-8.
[http://dx.doi.org/10.1620/tjem.223.113] [PMID: 21263211]
[57]
Edghill EL, Flanagan SE, Patch AM, et al. Neonatal Diabetes International Collaborative Group. 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): 1034-42.
[http://dx.doi.org/10.2337/db07-1405] [PMID: 18162506]
[58]
Molven A, Ringdal M, Nordbø AM, et al. Norwegian Childhood Diabetes Study Group. Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes. Diabetes 2008; 57(4): 1131-5.
[http://dx.doi.org/10.2337/db07-1467] [PMID: 18192540]
[59]
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(34): 14460-5.
[http://dx.doi.org/10.1073/pnas.0906474106] [PMID: 19667185]
[60]
Bowman P, Flanagan SE, Edghill EL, et al. Heterozygous ABCC8 mutations are a cause of MODY. Diabetologia 2012; 55(1): 123-7.
[http://dx.doi.org/10.1007/s00125-011-2319-x] [PMID: 21989597]
[61]
Bonnefond A, Philippe J, Durand E, et al. Whole-exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene. PLoS One 2012; 7(6)e37423
[http://dx.doi.org/10.1371/journal.pone.0037423]] [PMID: 22701567]
[62]
Yorifuji T, Nagashima K, Kurokawa K, et al. The C42R mutation in the Kir6.2 (KCNJ11) gene as a cause of transient neonatal diabetes, childhood diabetes, or later-onset, apparently type 2 diabetes mellitus. J Clin Endocrinol Metab 2005; 90(6): 3174-8.
[http://dx.doi.org/10.1210/jc.2005-0096] [PMID: 15784703]
[63]
Prudente S, Jungtrakoon P, Marucci A, et al. Loss-of-Function Mutations in APPL1 in Familial Diabetes Mellitus. Am J Hum Genet 2015; 97(1): 177-85.
[http://dx.doi.org/10.1016/j.ajhg.2015.05.011] [PMID: 26073777]
[64]
Naylor RN, Greeley SA, Bell GI, Philipson LH. Genetics and pathophysiology of neonatal diabetes mellitus. J Diabetes Investig 2011; 2(3): 158-69.
[http://dx.doi.org/10.1111/j.2040-1124.2011.00106.x] [PMID: 24843477]
[65]
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): 1359-66.
[http://dx.doi.org/10.2337/diabetes.49.8.1359] [PMID: 10923638]
[66]
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): 2381-5.
[http://dx.doi.org/10.1007/s00125-012-2595-0] [PMID: 22660720]
[67]
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): 339-48.
[http://dx.doi.org/10.1172/JCI200419876] [PMID: 15286800]
[68]
Boonen SE, Mackay DJ, Hahnemann JM, et al. Transient neonatal diabetes, ZFP57, and hypomethylation of multiple imprinted loci: a detailed follow-up. Diabetes Care 2013; 36(3): 505-12.
[http://dx.doi.org/10.2337/dc12-0700] [PMID: 23150280]
[69]
Touati A, Errea-Dorronsoro J, Nouri S, Halleb Y, Pereda A, Mahdhaoui N, et al. Transient neonatal diabetes mellitus and hypomethylation at additional imprinted loci: novel ZFP57 mutation and review on the literature. Acta Diabetol 2018.
[PMID: 30315371]
[70]
Bak M, Boonen SE, Dahl C, et al. Genome-wide DNA methylation analysis of transient neonatal diabetes type 1 patients with mutations in ZFP57. BMC Med Genet 2016; 17: 29.
[http://dx.doi.org/10.1186/s12881-016-0292-4] [PMID: 27075368]
[71]
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): 824-30.
[http://dx.doi.org/10.1038/sj.ejhg.5201629] [PMID: 16670688]
[72]
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): 456-66.
[http://dx.doi.org/10.1056/NEJMoa055068] [PMID: 16885549]
[73]
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): 375-82.
[http://dx.doi.org/10.1086/519174] [PMID: 17668386]
[74]
Støy J, Edghill EL, Flanagan SE, et al. Neonatal Diabetes International Collaborative Group. Insulin gene mutations as a cause of permanent neonatal diabetes. Proc Natl Acad Sci USA 2007; 104(38): 15040-4.
[http://dx.doi.org/10.1073/pnas.0707291104] [PMID: 17855560]
[75]
Njølstad PR, Søvik O, Cuesta-Muñoz A, et al. Neonatal diabetes mellitus due to complete glucokinase deficiency. N Engl J Med 2001; 344(21): 1588-92.
[http://dx.doi.org/10.1056/NEJM200105243442104] [PMID: 11372010]
[76]
Ballinger SW, Shoffner JM, Hedaya EV, et al. Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletion. Nat Genet 1992; 1(1): 11-5.
[http://dx.doi.org/10.1038/ng0492-11] [PMID: 1301992]
[77]
Tsukuda K, Suzuki Y, Kameoka K, et al. Screening of patients with maternally transmitted diabetes for mitochondrial gene mutations in the tRNA[Leu(UUR)] region. Diabet Med 1997; 14(12): 1032-7.
[http://dx.doi.org/10.1002/(SICI)1096-9136(199712)14:12<1032:AID-DIA504>3.0.CO;2-Y] [PMID: 9455930]
[78]
Wittenhagen LM, Kelley SO. Dimerization of a pathogenic human mitochondrial tRNA. Nat Struct Biol 2002; 9(8): 586-90.
[http://dx.doi.org/10.1038/nsb820] [PMID: 12101407]
[79]
Liu CY, Lee CF, Hong CH, Wei YH. Mitochondrial DNA mutation and depletion increase the susceptibility of human cells to apoptosis. Ann N Y Acad Sci 2004; 1011: 133-45.
[http://dx.doi.org/10.1196/annals.1293.014] [PMID: 15126291]
[80]
Remes AM, Majamaa K, Herva R, Hassinen IE. Adult-onset diabetes mellitus and neurosensory hearing loss in maternal relatives of MELAS patients in a family with the tRNA(Leu(UUR)) mutation. Neurology 1993; 43(5): 1015-20.
[http://dx.doi.org/10.1212/WNL.43.5.1015] [PMID: 8492919]
[81]
Tattersall RB. Mild familial diabetes with dominant inheritance. Q J Med 1974; 43(170): 339-57.
[PMID: 4212169]
[82]
Shields BM, Shepherd M, Hudson M, et al. UNITED study team. population-based assessment of a biomarker-based screening pathway to aid diagnosis of monogenic diabetes in young-onset patients. Diabetes Care 2017; 40(8): 1017-25.
[http://dx.doi.org/10.2337/dc17-0224] [PMID: 28701371]
[83]
DiMeglio LA, Evans-Molina C, Oram RA. Type 1 diabetes. Lancet 2018; 391(10138): 2449-62.
[http://dx.doi.org/10.1016/S0140-6736(18)31320-5] [PMID: 29916386]
[84]
Parkkola A, Härkönen T, Ryhänen SJ, Ilonen J, Knip M. Finnish Pediatric Diabetes Register. Extended family history of type 1 diabetes and phenotype and genotype of newly diagnosed children. Diabetes Care 2013; 36(2): 348-54.
[http://dx.doi.org/10.2337/dc12-0445] [PMID: 23033245]
[85]
Thanabalasingham G, Owen KR. Diagnosis and management of maturity onset diabetes of the young (MODY). BMJ 2011; 343: d6044.
[http://dx.doi.org/10.1136/bmj.d6044] [PMID: 22012810]
[86]
Hattersley AT, Patel KA. Precision diabetes: learning from monogenic diabetes. Diabetologia 2017; 60(5): 769-77.
[http://dx.doi.org/10.1007/s00125-017-4226-2] [PMID: 28314945]
[87]
Oram RA, Jones AG, Besser RE, et al. The majority of patients with long-duration type 1 diabetes are insulin microsecretors and have functioning beta cells. Diabetologia 2014; 57(1): 187-91.
[http://dx.doi.org/10.1007/s00125-013-3067-x] [PMID: 24121625]
[88]
Naylor R, Philipson LH. Who should have genetic testing for maturity-onset diabetes of the young? Clin Endocrinol (Oxf) 2011; 75(4): 422-6.
[http://dx.doi.org/10.1111/j.1365-2265.2011.04049.x] [PMID: 21521318]
[89]
Besser RE, Shepherd MH, McDonald TJ, et al. Urinary C-peptide creatinine ratio is a practical outpatient tool for identifying hepatocyte nuclear factor 1-alpha/hepatocyte nuclear factor 4-alpha maturity-onset diabetes of the young from long-duration type 1 diabetes. Diabetes Care 2011; 34(2): 286-91.
[http://dx.doi.org/10.2337/dc10-1293] [PMID: 21270186]
[90]
Shepherd M, Shields B, Hammersley S, et al. UNITED Team. 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): 1879-88.
[http://dx.doi.org/10.2337/dc16-0645] [PMID: 27271189]
[91]
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): 1958-63.
[http://dx.doi.org/10.1007/s00125-013-2962-5] [PMID: 23771172]
[92]
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): 957-63.
[http://dx.doi.org/10.1016/S0140-6736(15)60098-8] [PMID: 26231457]
[93]
Althari S, Gloyn AL. When is it MODY? Challenges in the Interpretation of Sequence Variants in MODY Genes. Rev Diabet Stud 2015; 12(3-4): 330-48.
[http://dx.doi.org/10.1900/RDS.2015.12.330] [PMID: 27111119]
[94]
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): 480-4.
[http://dx.doi.org/10.1007/s00125-013-3119-2] [PMID: 24323243]
[95]
Flannick J, Johansson S, Njølstad PR. Common and rare forms of diabetes mellitus: towards a continuum of diabetes subtypes. Nat Rev Endocrinol 2016; 12(7): 394-406.
[http://dx.doi.org/10.1038/nrendo.2016.50] [PMID: 27080136]
[96]
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): 2504-8.
[http://dx.doi.org/10.1007/s00125-010-1799-4] [PMID: 20499044]
[97]
SIFT Available at:. http://sift.jcvi.org/%0D
[98]
Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 2009; 4(7): 1073-81.
[http://dx.doi.org/10.1038/nprot.2009.86] [PMID: 19561590]
[99]
Align GVGD - University of utah Available at:. http://agvgd.hci.utah.edu/
[100]
Adzhubei IA, Schmidt S, Peshkin L, et al. A method and server for predicting damaging missense mutations. Nat Methods 2010; 7(4): 248-9.
[http://dx.doi.org/10.1038/nmeth0410-248] [PMID: 20354512]
[101]
PolyPhen-2: prediction of functional effects of human nsSNPs. Available at: http://genetics.bwh.harvard.edu/pph2/
[102]
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): 1383-92.
[http://dx.doi.org/10.2337/dc14-2769] [PMID: 26106223]
[103]
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): 279-86.
[http://dx.doi.org/10.1001/jama.2013.283980] [PMID: 24430320]
[104]
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): 1275-81.
[http://dx.doi.org/10.1016/S0140-6736(03)14571-0] [PMID: 14575972]
[105]
Gach A, Wyka K, Pietrzak I, Wegner O, Malecki MT, Mlynarski W. Neonatal diabetes in a child positive for islet cell antibodies at onset and Kir6.2 activating mutation. Diabetes Res Clin Pract 2009; 86(2): e25-7.
[http://dx.doi.org/10.1016/j.diabres.2009.07.011] [PMID: 19692135]
[106]
Beltrand J, Elie C, Busiah K, et al. GlidKir Study Group. Sulfonylurea Therapy Benefits Neurological and Psychomotor Functions in Patients With Neonatal Diabetes Owing to Potassium Channel Mutations. Diabetes Care 2015; 38(11): 2033-41.
[http://dx.doi.org/10.2337/dc15-0837] [PMID: 26438614]
[107]
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): 2503-13.
[http://dx.doi.org/10.2337/diabetes.54.9.2503] [PMID: 16123337]
[108]
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): 1054-61.
[http://dx.doi.org/10.1210/jc.2007-1826] [PMID: 18073297]
[109]
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): 203-7.
[http://dx.doi.org/10.1111/j.1399-5448.2009.00548.x] [PMID: 19686306]
[110]
Oka Y, Katagiri H, Yazaki Y, Murase T, Kobayashi T. Mitochondrial gene mutation in islet-cell-antibody-positive patients who were initially non-insulin-dependent diabetics. Lancet 1993; 342(8870): 527-8.
[http://dx.doi.org/10.1016/0140-6736(93)91649-7] [PMID: 8102670]
[111]
Huang CN, Jee SH, Hwang JJ, Kuo YF, Chuang LM. Autoimmune IDDM in a sporadic MELAS patient with mitochondrial tRNA(Leu(UUR)) mutation. Clin Endocrinol (Oxf) 1998; 49(2): 265-70.
[http://dx.doi.org/10.1046/j.1365-2265.1998.00455.x] [PMID: 9828917]
[112]
Murphy R, Turnbull DM, Walker M, Hattersley AT. Clinical features, diagnosis and management of maternally inherited diabetes and deafness (MIDD) associated with the 3243A>G mitochondrial point mutation. Diabet Med 2008; 25(4): 383-99.
[http://dx.doi.org/10.1111/j.1464-5491.2008.02359.x] [PMID: 18294221]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 8
Year: 2020
Page: [807 - 819]
Pages: 13
DOI: 10.2174/1573399816666191230114352
Price: $65

Article Metrics

PDF: 44
HTML: 4