Monogenic diabetes.
Journal
Nature reviews. Disease primers
ISSN: 2056-676X
Titre abrégé: Nat Rev Dis Primers
Pays: England
ID NLM: 101672103
Informations de publication
Date de publication:
09 03 2023
09 03 2023
Historique:
accepted:
18
01
2023
entrez:
9
3
2023
pubmed:
10
3
2023
medline:
14
3
2023
Statut:
epublish
Résumé
Monogenic diabetes includes several clinical conditions generally characterized by early-onset diabetes, such as neonatal diabetes, maturity-onset diabetes of the young (MODY) and various diabetes-associated syndromes. However, patients with apparent type 2 diabetes mellitus may actually have monogenic diabetes. Indeed, the same monogenic diabetes gene can contribute to different forms of diabetes with early or late onset, depending on the functional impact of the variant, and the same pathogenic variant can produce variable diabetes phenotypes, even in the same family. Monogenic diabetes is mostly caused by impaired function or development of pancreatic islets, with defective insulin secretion in the absence of obesity. The most prevalent form of monogenic diabetes is MODY, which may account for 0.5-5% of patients diagnosed with non-autoimmune diabetes but is probably underdiagnosed owing to insufficient genetic testing. Most patients with neonatal diabetes or MODY have autosomal dominant diabetes. More than 40 subtypes of monogenic diabetes have been identified to date, the most prevalent being deficiencies of GCK and HNF1A. Precision medicine approaches (including specific treatments for hyperglycaemia, monitoring associated extra-pancreatic phenotypes and/or following up clinical trajectories, especially during pregnancy) are available for some forms of monogenic diabetes (including GCK- and HNF1A-diabetes) and increase patients' quality of life. Next-generation sequencing has made genetic diagnosis affordable, enabling effective genomic medicine in monogenic diabetes.
Identifiants
pubmed: 36894549
doi: 10.1038/s41572-023-00421-w
pii: 10.1038/s41572-023-00421-w
doi:
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12Informations de copyright
© 2023. Crown.
Références
Riddle, M. C. et al. Monogenic diabetes: from genetic insights to population-based precision in care. reflections from a diabetes care editors’ expert forum. Diabetes Care 43, 3117–3128 (2020).
pubmed: 33560999
pmcid: 8162450
doi: 10.2337/dci20-0065
Froguel, P. et al. Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulin-dependent diabetes mellitus. Nature 356, 162–164 (1992).
pubmed: 1545870
doi: 10.1038/356162a0
Vionnet, N. et al. Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus. Nature 356, 721–722 (1992). Study identifying pathogenic mutations in GCK as leading to one of the most prevalent forms of monogenic diabetes.
pubmed: 1570017
doi: 10.1038/356721a0
American Diabetes Association Professional Practice Committee. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes — 2022. Diabetes Care 45 (Suppl. 1), S17–S38 (2022).
doi: 10.2337/dc22-S002
Bonnefond, A. et al. Pathogenic variants in actionable MODY genes are associated with type 2 diabetes. Nat. Metab. 2, 1126–1134 (2020). A study that highlights the incomplete penetrance of pathogenic mutations in monogenic diabetes genes, which are even found in patients with suspected typical T2DM.
pubmed: 33046911
doi: 10.1038/s42255-020-00294-3
Ahlqvist, E. et al. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol. 6, 361–369 (2018).
pubmed: 29503172
doi: 10.1016/S2213-8587(18)30051-2
Bonnefond, A. & Froguel, P. Clustering for a better prediction of type 2 diabetes mellitus. Nat. Rev. Endocrinol. 17, 193–194 (2021).
pubmed: 33526906
doi: 10.1038/s41574-021-00475-4
Yang, Y. & Chan, L. Monogenic diabetes: what it teaches us on the common forms of type 1 and type 2 diabetes. Endocr. Rev. 37, 190–222 (2016).
pubmed: 27035557
pmcid: 4890265
doi: 10.1210/er.2015-1116
Vaxillaire, M., Froguel, P. & Bonnefond, A. How recent advances in genomics improve precision diagnosis and personalized care of maturity-onset diabetes of the young. Curr. Diabetes Rep. 19, 79 (2019).
doi: 10.1007/s11892-019-1202-x
Shields, B. M. et al. Maturity-onset diabetes of the young (MODY): how many cases are we missing? Diabetologia 53, 2504–2508 (2010).
pubmed: 20499044
doi: 10.1007/s00125-010-1799-4
Donath, X. et al. Next-generation sequencing identifies monogenic diabetes in 16% of patients with late adolescence/adult-onset diabetes selected on a clinical basis: a cross-sectional analysis. BMC Med. 17, 132 (2019).
pubmed: 31291970
pmcid: 6621990
doi: 10.1186/s12916-019-1363-0
Vaxillaire, M. et al. Monogenic diabetes characteristics in a transnational multicenter study from Mediterranean countries. Diabetes Res. Clin. Pract. 171, 108553 (2021).
pubmed: 33242514
doi: 10.1016/j.diabres.2020.108553
Mohan, V. et al. Comprehensive genomic analysis identifies pathogenic variants in maturity-onset diabetes of the young (MODY) patients in South India. BMC Med. Genet. 19, 22 (2018).
pubmed: 29439679
pmcid: 5811965
doi: 10.1186/s12881-018-0528-6
Park, S. S. et al. Identifying pathogenic variants of monogenic diabetes using targeted panel sequencing in an East Asian population. J. Clin. Endocrinol. Metab. https://doi.org/10.1210/jc.2018-02397 (2019).
doi: 10.1210/jc.2018-02397
pubmed: 31498870
pmcid: 7069551
Breidbart, E. et al. Frequency and characterization of mutations in genes in a large cohort of patients referred to MODY registry. J. Pediatr. Endocrinol. Metab. 34, 633–638 (2021).
pubmed: 33852230
pmcid: 8970616
doi: 10.1515/jpem-2020-0501
Pezzilli, S. et al. Pathogenic variants of MODY-genes in adult patients with early-onset type 2 diabetes. Acta Diabetol. 59, 747–750 (2022).
pubmed: 35112188
doi: 10.1007/s00592-021-01847-y
Flannick, J. et al. Assessing the phenotypic effects in the general population of rare variants in genes for a dominant Mendelian form of diabetes. Nat. Genet. 45, 1380–1385 (2013).
pubmed: 24097065
pmcid: 4051627
doi: 10.1038/ng.2794
Mirshahi, U. L. et al. Reduced penetrance of MODY-associated HNF1A/HNF4A variants but not GCK variants in clinically unselected cohorts. Am. J. Hum. Genet. 109, 2018–2028 (2022).
pubmed: 36257325
pmcid: 9674944
doi: 10.1016/j.ajhg.2022.09.014
Da Silva Xavier, G. The cells of the islets of Langerhans. J. Clin. Med. 7, E54 (2018).
doi: 10.3390/jcm7030054
Yamagata, K. et al. Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3). Nature 384, 455–458 (1996). Study identifying pathogenic mutations in HNF1A as leading to one of the most prevalent forms of monogenic diabetes.
pubmed: 8945470
doi: 10.1038/384455a0
Yamagata, K. et al. Mutations in the hepatocyte nuclear factor-4α gene in maturity-onset diabetes of the young (MODY1). Nature 384, 458–460 (1996).
pubmed: 8945471
doi: 10.1038/384458a0
Raeder, H. et al. Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction. Nat. Genet. 38, 54–62 (2006).
pubmed: 16369531
doi: 10.1038/ng1708
Malikova, J. et al. Functional analyses of HNF1A-MODY variants refine the interpretation of identified sequence variants. J. Clin. Endocrinol. Metab. 105, dgaa051 (2020).
pubmed: 32017842
doi: 10.1210/clinem/dgaa051
Li, L.-M., Jiang, B.-G. & Sun, L.-L. HNF1A: from monogenic diabetes to type 2 diabetes and gestational diabetes mellitus. Front. Endocrinol. 13, 829565 (2022).
doi: 10.3389/fendo.2022.829565
Bonnefond, A. et al. GATA6 inactivating mutations are associated with heart defects and, inconsistently, with pancreatic agenesis and diabetes. Diabetologia 55, 2845–2847 (2012).
pubmed: 22806356
doi: 10.1007/s00125-012-2645-7
Jonsson, J., Carlsson, L., Edlund, T. & Edlund, H. Insulin-promoter-factor 1 is required for pancreas development in mice. Nature 371, 606–609 (1994).
pubmed: 7935793
doi: 10.1038/371606a0
Duque, M., Amorim, J. P. & Bessa, J. Ptf1a function and transcriptional cis-regulation, a cornerstone in vertebrate pancreas development. FEBS J. 289, 5121–5136 (2022).
pubmed: 34125483
doi: 10.1111/febs.16075
Tiyaboonchai, A. et al. GATA6 plays an important role in the induction of human definitive endoderm, development of the pancreas, and functionality of pancreatic β cells. Stem Cell Rep. 8, 589–604 (2017).
doi: 10.1016/j.stemcr.2016.12.026
Rouzier, C. et al. A novel CISD2 mutation associated with a classical Wolfram syndrome phenotype alters Ca
pubmed: 28335035
pmcid: 5411739
doi: 10.1093/hmg/ddx060
Shrestha, N., De Franco, E., Arvan, P. & Cnop, M. Pathological β-cell endoplasmic reticulum stress in type 2 diabetes: current evidence. Front. Endocrinol. 12, 650158 (2021).
doi: 10.3389/fendo.2021.650158
Graff, S. M. et al. A KCNK16 mutation causing TALK-1 gain-of-function is associated with maturity-onset diabetes of the young. JCI Insight 6, e138057 (2021).
pubmed: 34032641
pmcid: 8410089
doi: 10.1172/jci.insight.138057
Santer, R. et al. Mutations in GLUT2, the gene for the liver-type glucose transporter, in patients with Fanconi-Bickel syndrome. Nat. Genet. 17, 324–326 (1997).
pubmed: 9354798
doi: 10.1038/ng1197-324
Labay, V. et al. Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness. Nat. Genet. 22, 300–304 (1999).
pubmed: 10391221
doi: 10.1038/10372
Jungtrakoon, P. et al. Loss-of-function mutation in thiamine transporter 1 in a family with autosomal dominant diabetes. Diabetes 68, 1084–1093 (2019).
pubmed: 30833467
pmcid: 6477897
doi: 10.2337/db17-0821
Mancuso, M. et al. The m.3243A>G mitochondrial DNA mutation and related phenotypes. A matter of gender? J. Neurol. 261, 504–510 (2014).
pubmed: 24375076
doi: 10.1007/s00415-013-7225-3
Pickett, S. J. et al. Phenotypic heterogeneity in m.3243A>G mitochondrial disease: the role of nuclear factors. Ann. Clin. Transl. Neurol. 5, 333–345 (2018).
pubmed: 29560378
pmcid: 5846390
doi: 10.1002/acn3.532
Vaxillaire, M. & Froguel, P. Monogenic diabetes in the young, pharmacogenetics and relevance to multifactorial forms of type 2 diabetes. Endocr. Rev. 29, 254–264 (2008).
pubmed: 18436708
doi: 10.1210/er.2007-0024
Raimondo, A. et al. Phenotypic severity of homozygous GCK mutations causing neonatal or childhood-onset diabetes is primarily mediated through effects on protein stability. Hum. Mol. Genet. 23, 6432–6440 (2014).
pubmed: 25015100
pmcid: 4240195
doi: 10.1093/hmg/ddu360
Rees, M. G. et al. A panel of diverse assays to interrogate the interaction between glucokinase and glucokinase regulatory protein, two vital proteins in human disease. PLoS ONE 9, e89335 (2014).
pubmed: 24586696
pmcid: 3929664
doi: 10.1371/journal.pone.0089335
Njølstad, P. R. et al. Neonatal diabetes mellitus due to complete glucokinase deficiency. N. Engl. J. Med. 344, 1588–1592 (2001).
pubmed: 11372010
doi: 10.1056/NEJM200105243442104
Meur, G. et al. Insulin gene mutations resulting in early-onset diabetes: marked differences in clinical presentation, metabolic status, and pathogenic effect through endoplasmic reticulum retention. Diabetes 59, 653–661 (2010).
pubmed: 20007936
doi: 10.2337/db09-1091
Garin, I. et al. Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis. Proc. Natl Acad. Sci. USA 107, 3105–3110 (2010).
pubmed: 20133622
pmcid: 2840338
doi: 10.1073/pnas.0910533107
Bonnefond, A. et al. Disruption of a novel Kruppel-like transcription factor p300-regulated pathway for insulin biosynthesis revealed by studies of the c.-331 INS mutation found in neonatal diabetes mellitus. J. Biol. Chem. 286, 28414–28424 (2011).
pubmed: 21592955
pmcid: 3151084
doi: 10.1074/jbc.M110.215822
Johansson, B. B. et al. The role of the carboxyl ester lipase (CEL) gene in pancreatic disease. Pancreatology 18, 12–19 (2018).
pubmed: 29233499
doi: 10.1016/j.pan.2017.12.001
Kahraman, S. et al. Abnormal exocrine-endocrine cell cross-talk promotes β-cell dysfunction and loss in MODY8. Nat. Metab. 4, 76–89 (2022).
pubmed: 35058633
doi: 10.1038/s42255-021-00516-2
Tattersall, R. B. & Fajans, S. S. A difference between the inheritance of classical juvenile-onset and maturity-onset type diabetes of young people. Diabetes 24, 44–53 (1975).
pubmed: 1122063
doi: 10.2337/diab.24.1.44
Steele, A. M. et al. Prevalence of vascular complications among patients with glucokinase mutations and prolonged, mild hyperglycemia. JAMA 311, 279–286 (2014). A study that showed a very low prevalence of vascular complications in patients with long-term dominant GCK-diabetes.
pubmed: 24430320
doi: 10.1001/jama.2013.283980
Di Paola, R., Marucci, A. & Trischitta, V. The need to increase clinical skills and change the genetic testing strategy for monogenic diabetes. Diabetes 71, 379–380 (2022).
pubmed: 35196390
doi: 10.2337/dbi21-0037
Zhang, H., Colclough, K., Gloyn, A. L. & Pollin, T. I. Monogenic diabetes: a gateway to precision medicine in diabetes. J. Clin. Invest. 131, 142244 (2021).
pubmed: 33529164
doi: 10.1172/JCI142244
Kleinberger, J. W. et al. Monogenic diabetes in overweight and obese youth diagnosed with type 2 diabetes: the TODAY clinical trial. Genet. Med. 20, 583–590 (2018).
pubmed: 29758564
doi: 10.1038/gim.2017.150
Thanabalasingham, G. et al. Systematic assessment of etiology in adults with a clinical diagnosis of young-onset type 2 diabetes is a successful strategy for identifying maturity-onset diabetes of the young. Diabetes Care 35, 1206–1212 (2012).
pubmed: 22432108
pmcid: 3357216
doi: 10.2337/dc11-1243
Flannick, J., Johansson, S. & Njølstad, P. R. Common and rare forms of diabetes mellitus: towards a continuum of diabetes subtypes. Nat. Rev. Endocrinol. 12, 394–406 (2016).
pubmed: 27080136
doi: 10.1038/nrendo.2016.50
Shaw-Smith, C. et al. GATA4 mutations are a cause of neonatal and childhood-onset diabetes. Diabetes 63, 2888–2894 (2014).
pubmed: 24696446
doi: 10.2337/db14-0061
Bonnefond, A. et al. Whole-exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene. PLoS ONE 7, e37423 (2012).
pubmed: 22701567
pmcid: 3372463
doi: 10.1371/journal.pone.0037423
Kettunen, J. L. T. et al. A multigenerational study on phenotypic consequences of the most common causal variant of HNF1A-MODY. Diabetologia 65, 632–643 (2022).
pubmed: 34951657
doi: 10.1007/s00125-021-05631-z
Saint-Martin, C., Bouvet, D., Bastide, M. & Bellanné-Chantelot, C. Gene panel sequencing of patients with monogenic diabetes brings to light genes typically associated with syndromic presentations. Diabetes 71, 578–584 (2022).
pubmed: 34556497
doi: 10.2337/db21-0520
Colclough, K., Ellard, S., Hattersley, A. & Patel, K. Syndromic monogenic diabetes genes should be tested in patients with a clinical suspicion of maturity-onset diabetes of the young. Diabetes 71, 530–537 (2022). Saint-Martin, C. et al. and Colclough, K. et al. highlight the incomplete penetrance of pathogenetic mutations in syndromic monogenic diabetes genes; indeed, these mutations have been found in patients with suspected non-syndromic monogenic diabetes.
pubmed: 34789499
doi: 10.2337/db21-0517
Patel, K. A. et al. Systematic genetic testing for recessively inherited monogenic diabetes: a cross-sectional study in paediatric diabetes clinics. Diabetologia 65, 336–342 (2022).
pubmed: 34686905
doi: 10.1007/s00125-021-05597-y
Bonnefond, A. & Semple, R. K. Achievements, prospects and challenges in precision care for monogenic insulin-deficient and insulin-resistant diabetes. Diabetologia 65, 1782–1795 (2022).
pubmed: 35618782
pmcid: 9522735
doi: 10.1007/s00125-022-05720-7
Chapla, A. et al. Maturity onset diabetes of the young in India – a distinctive mutation pattern identified through targeted next-generation sequencing. Clin. Endocrinol. 82, 533–542 (2015).
doi: 10.1111/cen.12541
Shields, B. M. et al. The development and validation of a clinical prediction model to determine the probability of MODY in patients with young-onset diabetes. Diabetologia 55, 1265–1272 (2012).
pubmed: 22218698
pmcid: 3328676
doi: 10.1007/s00125-011-2418-8
Misra, S. et al. South Asian individuals with diabetes who are referred for MODY testing in the UK have a lower mutation pick-up rate than white European people. Diabetologia 59, 2262–2265 (2016).
pubmed: 27435864
pmcid: 5016539
doi: 10.1007/s00125-016-4056-7
Carroll, R. W. & Murphy, R. Monogenic diabetes: a diagnostic algorithm for clinicians. Genes 4, 522–535 (2013).
pubmed: 24705260
pmcid: 3927568
doi: 10.3390/genes4040522
Rubio-Cabezas, O. & Ellard, S. Diabetes mellitus in neonates and infants: genetic heterogeneity, clinical approach to diagnosis, and therapeutic options. Horm. Res. Paediatr. 80, 137–146 (2013).
pubmed: 24051999
pmcid: 3884170
doi: 10.1159/000354219
Pipatpolkai, T., Usher, S., Stansfeld, P. J. & Ashcroft, F. M. New insights into KATP channel gene mutations and neonatal diabetes mellitus. Nat. Rev. Endocrinol. 16, 378–393 (2020).
pubmed: 32376986
doi: 10.1038/s41574-020-0351-y
Shepherd, M. et al. Predictive genetic testing in maturity-onset diabetes of the young (MODY). Diabet. Med. 18, 417–421 (2001).
pubmed: 11472455
doi: 10.1046/j.1464-5491.2001.00447.x
Dubois-Laforgue, D. et al. Diabetes, associated clinical spectrum, long-term prognosis, and genotype/phenotype correlations in 201 adult patients with hepatocyte nuclear factor 1B (HNF1B) molecular defects. Diabetes Care 40, 1436–1443 (2017).
pubmed: 28420700
doi: 10.2337/dc16-2462
Shepherd, M. 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 39, 1879–1888 (2016).
pubmed: 27271189
doi: 10.2337/dc16-0645
Shields, B. M. et al. Population-based assessment of a biomarker-based screening pathway to aid diagnosis of monogenic diabetes in young-onset patients. Diabetes Care 40, 1017–1025 (2017).
pubmed: 28701371
doi: 10.2337/dc17-0224
Carlsson, A. et al. Absence of islet autoantibodies and modestly raised glucose values at diabetes diagnosis should lead to testing for MODY: lessons from a 5-year pediatric swedish national cohort study. Diabetes Care 43, 82–89 (2020).
pubmed: 31704690
doi: 10.2337/dc19-0747
Pihoker, C. 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. 98, 4055–4062 (2013).
pubmed: 23771925
pmcid: 3790621
doi: 10.1210/jc.2013-1279
Johnson, S. R. et al. Comprehensive genetic screening: the prevalence of maturity-onset diabetes of the young gene variants in a population-based childhood diabetes cohort. Pediatr. Diabetes 20, 57–64 (2019).
pubmed: 30191644
doi: 10.1111/pedi.12766
Dillon, O. J. et al. Exome sequencing has higher diagnostic yield compared to simulated disease-specific panels in children with suspected monogenic disorders. Eur. J. Hum. Genet. 26, 644–651 (2018).
pubmed: 29453417
pmcid: 5945679
doi: 10.1038/s41431-018-0099-1
Xue, Y., Ankala, A., Wilcox, W. R. & Hegde, M. R. Solving the molecular diagnostic testing conundrum for Mendelian disorders in the era of next-generation sequencing: single-gene, gene panel, or exome/genome sequencing. Genet. Med. 17, 444–451 (2015).
pubmed: 25232854
doi: 10.1038/gim.2014.122
Montagne, L. et al. CoDE-seq, an augmented whole-exome sequencing, enables the accurate detection of CNVs and mutations in Mendelian obesity and intellectual disability. Mol. Metab. 13, 1–9 (2018).
pubmed: 29784605
pmcid: 6026315
doi: 10.1016/j.molmet.2018.05.005
Richards, 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. 17, 405–424 (2015).
pubmed: 25741868
pmcid: 4544753
doi: 10.1038/gim.2015.30
Ellard, S., Colclough, K., Patel, K. A. & Hattersley, A. T. Prediction algorithms: pitfalls in interpreting genetic variants of autosomal dominant monogenic diabetes. J. Clin. Invest. 130, 14–16 (2020).
pubmed: 31815736
doi: 10.1172/JCI133516
Fajans, S. S. Heterogeneity of insulin responses in maturity-onset type diabetes (MOD) and in maturity-onset type diabetes of young people (MODY). Adv. Exp. Med. Biol. 119, 171–175 (1979).
pubmed: 495276
doi: 10.1007/978-1-4615-9110-8_25
Tattersall, R. B. & Mansell, P. I. Maturity onset-type diabetes of the young (MODY): one condition or many? Diabet. Med. 8, 402–410 (1991).
pubmed: 1830523
doi: 10.1111/j.1464-5491.1991.tb01623.x
Shepherd, M. H. et al. A UK nationwide prospective study of treatment change in MODY: genetic subtype and clinical characteristics predict optimal glycaemic control after discontinuing insulin and metformin. Diabetologia 61, 2520–2527 (2018).
pubmed: 30229274
pmcid: 6223847
doi: 10.1007/s00125-018-4728-6
Timsit, J., Ciangura, C., Dubois-Laforgue, D., Saint-Martin, C. & Bellanne-Chantelot, C. Pregnancy in women with monogenic diabetes due to pathogenic variants of the glucokinase gene: lessons and challenges. Front. Endocrinol. 12, 802423 (2021).
doi: 10.3389/fendo.2021.802423
Shields, B. M. et al. Mutations in the glucokinase gene of the fetus result in reduced placental weight. Diabetes Care 31, 753–757 (2008).
pubmed: 18184897
doi: 10.2337/dc07-1750
Urbanová, J., Brunerová, L., Nunes, M. & Brož, J. Identification of MODY among patients screened for gestational diabetes: a clinician’s guide. Arch. Gynecol. Obstet. 302, 305–314 (2020).
pubmed: 32495018
doi: 10.1007/s00404-020-05626-y
Bosselaar, M., Hattersley, A. T. & Tack, C. J. J. High sensitivity to sulphonylurea treatment in 2 patients with maturity-onset diabetes of the young type 3. Ned. Tijdschr. Geneeskd. 146, 726–729 (2002).
pubmed: 11980375
Stankute, I. et al. Systematic genetic study of youth with diabetes in a single country reveals the prevalence of diabetes subtypes, novel candidate genes, and response to precision therapy. Diabetes 69, 1065 (2020).
pubmed: 32086287
doi: 10.2337/db19-0974
Broome, D. T., Tekin, Z., Pantalone, K. M. & Mehta, A. E. Novel use of GLP-1 receptor agonist therapy in HNF4A-MODY. Diabetes Care 43, e65 (2020).
pubmed: 32265191
pmcid: 7245355
doi: 10.2337/dc20-0012
Haddouche, A. et al. Liver adenomatosis in patients with hepatocyte nuclear factor-1 alpha maturity onset diabetes of the young (HNF1A-MODY): clinical, radiological and pathological characteristics in a French series. J. Diabetes 12, 48–57 (2020).
pubmed: 31166087
doi: 10.1111/1753-0407.12959
Bowman, P. 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. 6, 637–646 (2018).
pubmed: 29880308
pmcid: 6058077
doi: 10.1016/S2213-8587(18)30106-2
Iafusco, D. et al. No beta cell desensitisation after a median of 68 months on glibenclamide therapy in patients with KCNJ11-associated permanent neonatal diabetes. Diabetologia 54, 2736–2738 (2011).
pubmed: 21822789
doi: 10.1007/s00125-011-2273-7
Babiker, T. et al. Successful transfer to sulfonylureas in KCNJ11 neonatal diabetes is determined by the mutation and duration of diabetes. Diabetologia 59, 1162–1166 (2016).
pubmed: 27033559
pmcid: 4869695
doi: 10.1007/s00125-016-3921-8
de Gouveia Buff Passone, C. et al. Sulfonylurea for improving neurological features in neonatal diabetes: a systematic review and meta-analyses. Pediatr. Diabetes 23, 675–692 (2022).
pubmed: 35657808
doi: 10.1111/pedi.13376
Aarthy, R. et al. Clinical features, complications and treatment of rarer forms of maturity-onset diabetes of the young (MODY) - a review. J. Diabetes Complicat. 35, 107640 (2021).
doi: 10.1016/j.jdiacomp.2020.107640
Urakami, T. Maturity-onset diabetes of the young (MODY): current perspectives on diagnosis and treatment. Diabetes Metab. Syndr. Obes. 12, 1047–1056 (2019).
pubmed: 31360071
pmcid: 6625604
doi: 10.2147/DMSO.S179793
Asif, M. The prevention and control the type-2 diabetes by changing lifestyle and dietary pattern. J. Educ. Health Promot. 3, 1 (2014).
pubmed: 24741641
pmcid: 3977406
doi: 10.4103/2277-9531.127541
Naylor, R. N. et al. Cost-effectiveness of MODY genetic testing: translating genomic advances into practical health applications. Diabetes Care 37, 202–209 (2014).
pubmed: 24026547
doi: 10.2337/dc13-0410
Greeley, S. A. W. et al. The cost-effectiveness of personalized genetic medicine: the case of genetic testing in neonatal diabetes. Diabetes Care 34, 622–627 (2011).
pubmed: 21273495
pmcid: 3041194
doi: 10.2337/dc10-1616
GoodSmith, M. S., Skandari, M. R., Huang, E. S. & Naylor, R. N. The impact of biomarker screening and cascade genetic testing on the cost-effectiveness of MODY genetic testing. Diabetes Care 42, 2247–2255 (2019).
pubmed: 31558549
pmcid: 6868460
doi: 10.2337/dc19-0486
Pasquali, L. et al. Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants. Nat. Genet. 46, 136–143 (2014).
pubmed: 24413736
pmcid: 3935450
doi: 10.1038/ng.2870
Gaulton, K. J. et al. Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci. Nat. Genet. 47, 1415–1425 (2015).
pubmed: 26551672
pmcid: 4666734
doi: 10.1038/ng.3437
Ndiaye, F. K. et al. Expression and functional assessment of candidate type 2 diabetes susceptibility genes identify four new genes contributing to human insulin secretion. Mol. Metab. 6, 459–470 (2017).
pubmed: 28580277
pmcid: 5444093
doi: 10.1016/j.molmet.2017.03.011
Khera, A. V. et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat. Genet. 50, 1219–1224 (2018).
pubmed: 30104762
pmcid: 6128408
doi: 10.1038/s41588-018-0183-z
Weedon, M. N. et al. Recessive mutations in a distal PTF1A enhancer cause isolated pancreatic agenesis. Nat. Genet. 46, 61–64 (2014).
pubmed: 24212882
doi: 10.1038/ng.2826
Rees, M. G. & Gloyn, A. L. Small molecular glucokinase activators: has another new anti-diabetic therapeutic lost favour? Br. J. Pharmacol. 168, 335–338 (2013).
pubmed: 22946641
doi: 10.1111/j.1476-5381.2012.02201.x
Sharma, P. et al. Targeting human Glucokinase for the treatment of type 2 diabetes: an overview of allosteric Glucokinase activators. J. Diabetes Metab. Disord. 21, 1129–1137 (2022).
pubmed: 35673438
doi: 10.1007/s40200-022-01019-x
Stoffers, D. A., Ferrer, J., Clarke, W. L. & Habener, J. F. Early-onset type-II diabetes mellitus (MODY4) linked to IPF1. Nat. Genet. 17, 138–139 (1997).
pubmed: 9326926
doi: 10.1038/ng1097-138
Horikawa, Y. et al. Mutation in hepatocyte nuclear factor-1 beta gene (TCF2) associated with MODY. Nat. Genet. 17, 384–385 (1997).
pubmed: 9398836
doi: 10.1038/ng1297-384
Malecki, M. T. et al. Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Nat. Genet. 23, 323–328 (1999).
pubmed: 10545951
doi: 10.1038/15500
Bowman, P. et al. Heterozygous ABCC8 mutations are a cause of MODY. Diabetologia 55, 123–127 (2012).
pubmed: 21989597
doi: 10.1007/s00125-011-2319-x
Bonnycastle, L. L. et al. Autosomal dominant diabetes arising from a Wolfram syndrome 1 mutation. Diabetes 62, 3943–3950 (2013).
pubmed: 23903355
pmcid: 3806620
doi: 10.2337/db13-0571
Igoillo-Esteve, M. et al. tRNA methyltransferase homolog gene TRMT10A mutation in young onset diabetes and primary microcephaly in humans. PLoS Genet. 9, e1003888 (2013).
pubmed: 24204302
pmcid: 3814312
doi: 10.1371/journal.pgen.1003888
Simaite, D. et al. Recessive mutations in PCBD1 cause a new type of early-onset diabetes. Diabetes 63, 3557–3564 (2014).
pubmed: 24848070
doi: 10.2337/db13-1784
Prudente, S. et al. Loss-of-function mutations in APPL1 in familial diabetes mellitus. Am. J. Hum. Genet. 97, 177–185 (2015).
pubmed: 26073777
pmcid: 4571002
doi: 10.1016/j.ajhg.2015.05.011
Patel, K. A. et al. Heterozygous RFX6 protein truncating variants are associated with MODY with reduced penetrance. Nat. Commun. 8, 888 (2017).
pubmed: 29026101
pmcid: 5638866
doi: 10.1038/s41467-017-00895-9
Iacovazzo, D. et al. MAFA missense mutation causes familial insulinomatosis and diabetes mellitus. Proc. Natl Acad. Sci. USA 115, 1027–1032 (2018).
pubmed: 29339498
pmcid: 5798333
doi: 10.1073/pnas.1712262115
Philippi, A. et al. Mutations and variants of ONECUT1 in diabetes. Nat. Med. 27, 1928–1940 (2021).
pubmed: 34663987
pmcid: 9356324
doi: 10.1038/s41591-021-01502-7
Yorifuji, T. et al. Neonatal diabetes mellitus and neonatal polycystic, dysplastic kidneys: phenotypically discordant recurrence of a mutation in the hepatocyte nuclear factor-1β gene due to germline mosaicism. J. Clin. Endocrinol. Metab. 89, 2905–2908 (2004).
pubmed: 15181075
doi: 10.1210/jc.2003-031828
Gloyn, A. L. et al. Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N. Engl. J. Med. 350, 1838–1849 (2004).
pubmed: 15115830
doi: 10.1056/NEJMoa032922
Babenko, A. P. et al. Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. N. Engl. J. Med. 355, 456–466 (2006).
pubmed: 16885549
doi: 10.1056/NEJMoa055068
Støy, J. et al. Insulin gene mutations as a cause of permanent neonatal diabetes. Proc. Natl Acad. Sci. USA 104, 15040–15044 (2007).
pubmed: 17855560
pmcid: 1986609
doi: 10.1073/pnas.0707291104
The International Pancreatic Agenesis Consortium. GATA6 haploinsufficiency causes pancreatic agenesis in humans. Nat. Genet. 44, 20–22 (2012).
doi: 10.1038/ng.1035
van den Ouweland, J. M. et al. Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. Nat. Genet. 1, 368–371 (1992).
pubmed: 1284550
doi: 10.1038/ng0892-368
Nagamine, K. et al. Positional cloning of the APECED gene. Nat. Genet. 17, 393–398 (1997).
pubmed: 9398839
doi: 10.1038/ng1297-393
Finnish-German APECED Consortium. An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nat. Genet. 17, 399–403 (1997).
doi: 10.1038/ng1297-399
Stoffers, D. A., Zinkin, N. T., Stanojevic, V., Clarke, W. L. & Habener, J. F. Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence. Nat. Genet. 15, 106–110 (1997).
pubmed: 8988180
doi: 10.1038/ng0197-106
Inoue, H. et al. A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). Nat. Genet. 20, 143–148 (1998).
pubmed: 9771706
doi: 10.1038/2441
De Franco, E. et al. Dominant ER stress-inducing WFS1 mutations underlie a genetic syndrome of neonatal/infancy-onset diabetes, congenital sensorineural deafness, and congenital cataracts. Diabetes 66, 2044–2053 (2017).
pubmed: 28468959
pmcid: 5482085
doi: 10.2337/db16-1296
Delépine, M. et al. EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott–Rallison syndrome. Nat. Genet. 25, 406–409 (2000).
pubmed: 10932183
doi: 10.1038/78085
Bennett, C. L. et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat. Genet. 27, 20–21 (2001).
pubmed: 11137993
doi: 10.1038/83713
Sellick, G. S. et al. Mutations in PTF1A cause pancreatic and cerebellar agenesis. Nat. Genet. 36, 1301–1305 (2004).
pubmed: 15543146
doi: 10.1038/ng1475
Senée, V. et al. Mutations in GLIS3 are responsible for a rare syndrome with neonatal diabetes mellitus and congenital hypothyroidism. Nat. Genet. 38, 682–687 (2006).
pubmed: 16715098
doi: 10.1038/ng1802
Yasuda, T. et al. PAX6 mutation as a genetic factor common to aniridia and glucose intolerance. Diabetes 51, 224–230 (2002).
pubmed: 11756345
doi: 10.2337/diabetes.51.1.224
Kofoed, E. M. et al. Growth hormone insensitivity associated with a STAT5b mutation. N. Engl. J. Med. 349, 1139–1147 (2003).
pubmed: 13679528
doi: 10.1056/NEJMoa022926
Amr, S. et al. A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. Am. J. Hum. Genet. 81, 673–683 (2007).
pubmed: 17846994
pmcid: 2227919
doi: 10.1086/520961
Smith, S. B. et al. Rfx6 directs islet formation and insulin production in mice and humans. Nature 463, 775–780 (2010).
pubmed: 20148032
pmcid: 2896718
doi: 10.1038/nature08748
Rubio-Cabezas, O. et al. Homozygous mutations in NEUROD1 are responsible for a novel syndrome of permanent neonatal diabetes and neurological abnormalities. Diabetes 59, 2326–2331 (2010).
pubmed: 20573748
pmcid: 2927956
doi: 10.2337/db10-0011
Rubio-Cabezas, O. et al. Permanent neonatal diabetes and enteric anendocrinosis associated with biallelic mutations in NEUROG3. Diabetes 60, 1349–1353 (2011).
pubmed: 21378176
pmcid: 3064109
doi: 10.2337/db10-1008
Poulton, C. J. et al. Microcephaly with simplified gyration, epilepsy, and infantile diabetes linked to inappropriate apoptosis of neural progenitors. Am. J. Hum. Genet. 89, 265–276 (2011).
pubmed: 21835305
pmcid: 3155199
doi: 10.1016/j.ajhg.2011.07.006
Boonen, S. E. et al. Transient neonatal diabetes, ZFP57, and hypomethylation of multiple imprinted loci: a detailed follow-up. Diabetes Care 36, 505–512 (2013).
pubmed: 23150280
pmcid: 3579357
doi: 10.2337/dc12-0700
Bonnefond, A. et al. Transcription factor gene MNX1 is a novel cause of permanent neonatal diabetes in a consanguineous family. Diabetes Metab. 39, 276–280 (2013).
pubmed: 23562494
doi: 10.1016/j.diabet.2013.02.007
Synofzik, M. et al. Absence of BiP co-chaperone DNAJC3 causes diabetes mellitus and multisystemic neurodegeneration. Am. J. Hum. Genet. 95, 689–697 (2014).
pubmed: 25466870
pmcid: 4259973
doi: 10.1016/j.ajhg.2014.10.013
Flanagan, S. E. et al. Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease. Nat. Genet. 46, 812–814 (2014).
pubmed: 25038750
pmcid: 4129488
doi: 10.1038/ng.3040
Flanagan, S. E. et al. Analysis of transcription factors key for mouse pancreatic development establishes NKX2-2 and MNX1 mutations as causes of neonatal diabetes in man. Cell Metab. 19, 146–154 (2014).
pubmed: 24411943
pmcid: 3887257
doi: 10.1016/j.cmet.2013.11.021
Kerns, S. L. et al. A novel variant in CDKN1C is associated with intrauterine growth restriction, short stature, and early-adulthood-onset diabetes. J. Clin. Endocrinol. Metab. 99, E2117–E2122 (2014).
pubmed: 25057881
pmcid: 4184067
doi: 10.1210/jc.2014-1949
Abdulkarim, B. et al. A missense mutation in PPP1R15B causes a syndrome including diabetes, short stature and microcephaly. Diabetes 64, 3951–3962 (2015).
pubmed: 26159176
pmcid: 4713904
doi: 10.2337/db15-0477
Johnson, M. B. et al. Recessively inherited LRBA mutations cause autoimmunity presenting as neonatal diabetes. Diabetes 66, 2316–2322 (2017).
pubmed: 28473463
doi: 10.2337/db17-0040
Şıklar, Z. et al. Monogenic diabetes not caused by mutations in mody genes: a very heterogenous group of diabetes. Exp. Clin. Endocrinol. Diabetes 126, 612–618 (2018).
pubmed: 29183106
doi: 10.1055/s-0043-120571
Stekelenburg, C. et al. Exome sequencing identifies a de novo FOXA2 variant in a patient with syndromic diabetes. Pediatr. Diabetes 20, 366–369 (2019).
pubmed: 30684292
doi: 10.1111/pedi.12814
De Franco, E. et al. A specific CNOT1 mutation results in a novel syndrome of pancreatic agenesis and holoprosencephaly through impaired pancreatic and neurological development. Am. J. Hum. Genet. 104, 985–989 (2019).
pubmed: 31006513
pmcid: 6506862
doi: 10.1016/j.ajhg.2019.03.018
De Franco, E. et al. YIPF5 mutations cause neonatal diabetes and microcephaly through endoplasmic reticulum stress. J. Clin. Invest. 130, 6338–6353 (2020).
pubmed: 33164986
pmcid: 7685733
doi: 10.1172/JCI141455
De Franco, E. et al. De novo mutations in EIF2B1 affecting eIF2 signaling cause neonatal/early onset diabetes and transient hepatic dysfunction. Diabetes 69, 477–483 (2020).
pubmed: 31882561
doi: 10.2337/db19-1029
Lekszas, C. et al. Biallelic TANGO1 mutations cause a novel syndromal disease due to hampered cellular collagen secretion. eLife 9, e51319 (2020).
pubmed: 32101163
pmcid: 7062462
doi: 10.7554/eLife.51319
Chaimowitz, N. S., Ebenezer, S. J., Hanson, I. C., Anderson, M. & Forbes, L. R. STAT1 gain of function, type 1 diabetes, and reversal with JAK inhibition. N. Engl. J. Med. 383, 1494–1496 (2020).
pubmed: 33027576
doi: 10.1056/NEJMc2022226
Montaser, H. et al. Loss of MANF causes childhood-onset syndromic diabetes due to increased endoplasmic reticulum stress. Diabetes 70, 1006–1018 (2021).
pubmed: 33500254
pmcid: 7610619
doi: 10.2337/db20-1174
Blodgett, D. M. et al. Novel observations from next-generation RNA sequencing of highly purified human adult and fetal islet cell subsets. Diabetes 64, 3172–3181 (2015).
pubmed: 25931473
pmcid: 4542439
doi: 10.2337/db15-0039
Alonso, L. et al. TIGER: The gene expression regulatory variation landscape of human pancreatic islets. Cell Rep. 37, 109807 (2021).
pubmed: 34644572
pmcid: 8864863
doi: 10.1016/j.celrep.2021.109807
Bansal, V. et al. Spectrum of mutations in monogenic diabetes genes identified from high-throughput DNA sequencing of 6888 individuals. BMC Med. 15, 213 (2017).
pubmed: 29207974
pmcid: 5717832
doi: 10.1186/s12916-017-0977-3
Goodrich, J. K. et al. Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes. Nat. Commun. 12, 3505 (2021).
pubmed: 34108472
pmcid: 8190084
doi: 10.1038/s41467-021-23556-4