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Cited by 23Genomics and Rare DiseasesDiabetes and associated disordersPancreatic function and diabetes

GCK-MODY in the US Monogenic Diabetes Registry: description of 27 unpublished variants

Open access
Sanyoura, May, Letourneau, Lisa, Knight Johnson, Amy E., del Gaudio, Daniela, Greeley, Siri Atma W., Philipson, Louis H., Naylor, Rochelle N.·2019·Diabetes Research and Clinical Practice
DOI 10.1016/j.diabres.2019.04.017PMC PMC6544496
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Abstract

We report on 134 unique GCK variants in 217 families, including 27 unpublished variants, identified in the US Monogenic Diabetes Registry in the last decade. Using ACMG guidelines, 26% were pathogenic, 56% likely pathogenic and 18% were of uncertain significance. Those with pathogenic variants had clinical features consistent with GCK-MODY.

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Crossref · 10.1016/j.diabres.2019.04.017

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  • Atypical diabetes is becoming increasingly difficult to precisely define in the absence of a definitive set of tests for either type 1 or type 2 diabetes.

    “although admittedly, atypical diabetes is becoming increasingly dif fi cult to precisely de fi ne in the absence of a de fi nitive set of tests for either type of diabetes (158 -160,163 -169)”

    From 2. Diagnosis and Classification of Diabetes: <i>Standards of Care in Diabetes—2024</i> (2024) · cites this paper as [158]

    The Introduction describes the clinical and genetic heterogeneity of MODY, and Materials and Methods describes clinical criteria and genetic testing for GCK-MODY. Neither section addresses whether atypical diabetes is becoming harder to define or whether definitive tests for type 1 and type 2 diabetes are lacking; searches for those points found no supporting passage in our copy. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

  • Diabetes occurring under 6 months of age is termed neonatal or congenital diabetes, and about 80-85% of cases can be found to have an underlying monogenic cause.

    “Diabetes occurring under 6 months of age is termed neonatal or congenital diabetes, and about 80 -85% of cases can be found to have an underlying monogenic cause (36,157 -160).”

    From 2. Diagnosis and Classification of Diabetes: <i>Standards of Care in Diabetes—2024</i> (2024) · cites this paper as [158]

    The Introduction describes GCK-MODY, including hyperglycemia present at birth, but does not define neonatal or congenital diabetes by onset before six months. Searches for that definition and the 80–85% monogenic-cause estimate found no supporting passage; neonatal diabetes appears only in a reference title (References, no page provided). (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • About 80-85% of neonatal diabetes cases can be found to have an underlying monogenic cause.

    “about 80-85% of cases can be found to have an underlying monogenic cause (36,(154)(155)(156)(157).”

    From 2. Diagnosis and classification of diabetes: standards of care in diabetes-2025 (2025) · cites this paper as [155]

    The Introduction discusses MODY and estimates that its subtypes account for about 2–5% of all diabetes cases; the Discussion reports the proportion of MODY cases involving GCK in this registry. Neither section gives a proportion of neonatal diabetes cases with a monogenic cause. Searches for neonatal diabetes and 80–85% found only a neonatal-diabetes study listed in the References, not the claimed estimate. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

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Cites

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Research works printed but not linked: 21

  1. [1]Fajans SS, Bell GI. MODY: history, genetics, pathophysiology, and clinical decision making. Diabetes Care. 2011; 34: 1878– 84.doi: 10.2337/dc11-0035. 21788644 PMC3142024 · DOI
  2. [2]Fendler W, Borowiec M, Baranowska-Jazwiecka A, Szadkowska A, Skala-Zamorowska E, Deja G, Prevalence of monogenic diabetes amongst Polish children after a nationwide genetic screening campaign. Diabetologia. 2012; 55: 2631– 5.doi: 10.1007/s00125-012-2621-2. 22782286 PMC3433657 · DOI
  3. [3]Irgens HU, Molnes J, Johansson BB, Ring dal M, Skrivarhaug T, Undlien DE, Prevalence of monogenic diabetes in the population-based Norwegian Childhood Diabetes Registry. Diabetologia. 2013; 56: 1512– 9.doi: 10.1007/s00125-013-2916-y. 23624530 · DOI
  4. [4]Johansson BB, Irgens HU, Molnes J, Sztromwasser P, Aukrust I, Juliusson PB, 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: 625– 35.doi: 10.1007/s00125-016-4167-1. 27913849 · DOI
  5. [6]Byrne MM, Sturis J, Clement K, Vionnet N, Pueyo ME, Stoffel M, Insulin secretory abnormalities in subjects with hyperglycemia due to glucokinase mutations. J Clin Invest. 1994; 93: 1120– 30.doi: 10.1172/JCI117064. 8132752 PMC294056 · DOI
  6. [7]Ellard S, Bellanne-Chantelot C, Hattersley AT, European Molecular Genetics Quality Network Mg. Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young. Diabetologia. 2008; 51: 546– 53.doi: 10.1007/s00125-008-0942-y. 18297260 PMC2270360 · DOI
  7. [8]Steele AM, Wensley KJ, Ellard S, Murphy R, Shepherd M, Colclough K, Use of HbA1c in the identification of patients with hyperglycaemia caused by a glucokinase mutation: observational case control studies. PLoS One. 2013; 8: e65326.doi: 10.1371/journal.pone.0065326. 23799006 PMC3683003 · DOI
  8. [9]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: 279– 86.doi: 10.1001/jama.2013.283980. 24430320 · DOI
  9. [10]Stenson PD, Ball EV, Mort M, Phillips AD, Shiel JA, Thomas NS, Human Gene Mutation Database (HGMD): 2003 update. Hum Mutat. 2003; 21: 577– 81.doi: 10.1002/humu.10212. 12754702 · DOI
  10. [11]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: 1230– 6.doi: 10.2337/dc13-2248. 24550216 · DOI
  11. [13]Greeley SA, Naylor RN, Cook LS, Tucker SE, Lipton RB, Philipson LH. Creation of the Web-based University of Chicago Monogenic Diabetes Registry: using technology to facilitate longitudinal study of rare subtypes of diabetes. J Diabetes Sci Technol. 2011; 5: 879– 86.doi: 10.1177/193229681100500409. 21880229 PMC3192593 · DOI
  12. [14]Alkorta-Aranburu G, Carmody D, Cheng YW, Nelakuditi V, Ma L, Dickens JT, Phenotypic heterogeneity in monogenic diabetes: the clinical and diagnostic utility of a gene panel-based next-generation sequencing approach. Mol Genet Metab. 2014; 113: 315– 20.doi: 10.1016/j.ymgme.2014.09.007. 25306193 PMC4756642 · DOI
  13. [15]Alkorta-Aranburu G, Sukhanova M, Carmody D, Hoffman T, Wysinger L, Keller-Ramey J, Improved molecular diagnosis of patients with neonatal diabetes using a combined next-generation sequencing and MS-MLPA approach. J Pediatr Endocrinol Metab. 2016; 29: 523– 31.doi: 10.1515/jpem-2015-0341. 26894574 · DOI
  14. [16]Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016; 536: 285– 91.doi: 10.1038/nature19057. 27535533 PMC5018207 · DOI · Paper page
  15. [19]Froguel P, Zouali H, Vionnet N, Velho G, Vaxillaire M, Sun F, Familial hyperglycemia due to mutations in glucokinase. Definition of a subtype of diabetes mellitus. N Engl J Med. 1993; 328: 697– 702.doi: 10.1056/NEJM199303113281005. 8433729 · DOI
  16. [20]Barrio R, Bellanne-Chantelot C, Moreno JC, Morel V, Calle H, Alonso M, Nine novel mutations in maturity-onset diabetes of the young (MODY) candidate genes in 22 Spanish families. J Clin Endocrinol Metab. 2002; 87: 2532– 9.doi: 10.1210/jcem.87.6.8530. 12050210 · DOI
  17. [21]Massa O, Meschi F, Cuesta-Munoz A, Caumo A, Cerutti F, Toni S, High prevalence of glucokinase mutations in Italian children with MODY. Influence on glucose tolerance, first-phase insulin response, insulin sensitivity and BMI. Diabetologia. 2001; 44: 898– 905 11508276
  18. [22]Codner E, Rocha A, Deng L, Martinez-Aguayo A, Godoy C, Mericq V, Mild fasting hyperglycemia in children: high rate of glucokinase mutations and some risk of developing type 1 diabetes mellitus. Pediatr Diabetes. 2009; 10: 382– 8.doi: 10.1111/j.1399-5448.2009.00499.x. 19309449 PMC2864306 · DOI
  19. [23]Sagen JV, Bjorkhaug L, Molnes J, Raeder H, Grevle L, Sovik O, Diagnostic screening of MODY2/GCK mutations in the Norwegian MODY Registry. Pediatr Diabetes. 2008; 9: 442– 9.doi: 10.1111/j.1399-5448.2008.00399.x. 18399931 · DOI
  20. [24]Dickens LT, Naylor RN. Clinical Management of Women with Monogenic Diabetes During Pregnancy. Curr Diab Rep. 2018; 18: 12.doi: 10.1007/s11892-018-0982-8. 29450745 PMC5908233 · DOI
  21. [25]Patel KA, Oram RA, Flanagan SE, De Franco E, Colclough K, Shepherd M, Type 1 Diabetes Genetic Risk Score: A Novel Tool to Discriminate Monogenic and Type 1 Diabetes. Diabetes. 2016; 65: 2094– 9.doi: 10.2337/db15-1690. 27207547 PMC4920219 · DOI

Cited by

Sorted by citations

Authors
Sanyoura, M., Letourneau, L., Knight Johnson, A. E., del Gaudio, D., Greeley, S. A. W., Philipson, L. H., & Naylor, R. N.
Affiliations
University of Chicago (US)
Corresponding author
Sanyoura, May
ORCID
Venue
Diabetes Research and Clinical Practice
Publisher
Elsevier BV
Published
2019-05
Volume
151
Pages
231-236
ISSN
0168-8227 (ISSN-L)
DOI
10.1016/j.diabres.2019.04.017
PMC
PMC6544496
OpenAlex
W2944420664
Cited by
23
References
4
Citations by year
2026: 2 · 2025: 1 · 2024: 5 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 6
FWCI
1.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes Research and Clinical Practice (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (R01DK104942, K23DK114564)
  • University of Chicago DRTC (P30DK020595)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
GCK-MODY, monogenic diabetes, pathogenic variants, variant interpretation, ACMG guidelines, clinical features
MeSH terms
Adolescent, Adult, Child, Diabetes Mellitus, Type 2, Female, Glucokinase, Humans, Male, Registries, United States, Young Adult

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