Skip to main content

12-08-2017 | Diagnosis | Case report | Article

A Case of Maturity Onset Diabetes of the Young (MODY3) in a Family with a Novel HNF1A Gene Mutation in Five Generations

Journal: Diabetes Therapy

Authors: A. K. Ovsyannikova, O. D. Rymar, D. E. Ivanoshchuk, Svetlana V. Mikhailova, E. V. Shakhtshneider, P. S. Orlov, E. S. Malakhina, M. I. Voevoda

Publisher: Springer Healthcare


Diabetes mellitus with autosomal dominant inheritance, i.e., maturity-onset diabetes of the young (MODY), is a genetic form of diabetes mellitus. The MODY phenotype is associated with gene mutations leading to pancreatic β-cell dysfunction. Here, we present the clinical case of a 50-year-old proband with familial diabetes mellitus in five generations (proband, her mother, grandmother, great-grandfather, and son). This disease is most likely associated with the novel Ser6Arg mutation in the HNF1A gene, which was identified in four family members. The mutation was not detected in MODY patients (126 subjects), in patients with type 2 diabetes mellitus (188 subjects), and in a general population sample (564 subjects).
Lachanse CH. Practical aspects of monogenic diabetes: a clinical point of view. Can J Diabetes. 2016;40:368–75. CrossRef
Rubio-Cabezas O, Hattersley AT, Njolstad PR, et al. The diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes. 2014;15(20):47–64. CrossRefPubMed
Fajans SS, Bell GI. MODY: history, genetics, pathophysiology, and clinical decision making. Diabetes Care. 2011;34(8):1878–84. CrossRefPubMedPubMedCentral
Stanik J, Dusatkova P, Cinek O, et al. De novo mutations of GCK, HNF1a and HNF 4a may be more frequent in MODY than previously assumed. Diabetologia. 2014;57:480–4. CrossRefPubMed
Voevoda MI, Ivanova AA, Shakhtshneider EV, et al. Molecular genetics of maturity-onset diabetes of the young. Ther Arch. 2016;88(4):117–24.
Pihoker C, Gilliam MK, 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;98:4055–62. CrossRefPubMedPubMedCentral
Agarwal SK, Khatri S, Prakash N, et al. Maturity onset diabetes of young. JIACM. 2002;3(3):271.
Thanabalasingham G, Pal A, Selwood MP, 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. 2012;35:1206–2012. CrossRefPubMedPubMedCentral
McDonald TJ, Ellard S. Maturity onset diabetes of the young: identification and diagnosis. Ann Clin Biochem. 2013;50(Pt 5):403–15. CrossRefPubMed
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. doi: 10.​1371/​journal.​pone.​0037423
Delvecchio M, Ludovico O, Menzaghi C, et al. Low prevalence of HNF1A mutations after molecular screening of multiple MODY genes in 58 Italian families recruited in the pediatric or adult diabetes clinic from a single Italian hospital. Diabetes Care. 2014;37:258–60. CrossRef
Thanabalasingham G, Owen KR. Diagnosis and management of maturity onset diabetes of the young (MODY). BMJ. 2011;343:d6044. doi: 10.​1136/​bmj.​d6044 CrossRef
Shields BM, Hicks S, Shepherd MH, et al. Maturity-onset diabetes of the young (MODY): how many cases are we missing? Diabetologia. 2010;53:2504–8. CrossRefPubMed
Kuraeva TL, Sechko EA, Eremina IA, Ivanova ON, Proko’ev SA. MODY3 in the child with type 2 diabetes mellitus phenotype: case report. Diabetes mellitus. 2013;2(59):88–93. CrossRef
Sambrook J, Russell DW. Purification of nucleic acids by extraction with phenol:chloroform. CSH Protoc. 2006;(1). doi: 10.​1101/​pdb.​prot4455
Mendel DB, Crabtree GR. HNF-1, a member of a novel class of dimerizing homeodomain proteins. J Biol Chem. 1991;266(2):677–80. PubMed
Adzhubei IA, Schmidt S, Peshkin L, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7:248–9. CrossRefPubMedPubMedCentral
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. CrossRefPubMed
Eide SA, Raeder H, Johansson S, et al. Prevalence of HNF1A (MODY3) mutations in a Norwegian population (the HUNT2 Study). Diabet Med. 2008;25(7):775–81. https://​doi.​org/​10.​1111/​j.​1464-5491.​2008.​02459.​x. CrossRefPubMed
Pajak A, Szafraniec K, Kubinova R, et al. Binge drinking and blood pressure: cross-sectional results of the HAPIEE Study. PLoS One. 2013;8(6):e65856. https://​doi.​org/​10.​1371/​journal.​pone.​0065856. CrossRefPubMedPubMedCentral
Ovsyannikova AK, Rymar OD, Shakhtshneider EV, et al. ABCC8-related maturity-onset diabetes of the young (MODY 12). Diabetes Ther. 2016;7:591–600. CrossRefPubMedPubMedCentral
Shields BM, Peters JL, Cooper C, et al. Is there an evidence base for the clinical features used to differentiate type 1 from type 2 diabetes? A systematic review of the literature. Diabetologia. 2014;57(11):439–40.
Shields BM, McDonald TJ, Ellard S, et al. The development and validation of a clinical prediction model to determine the probability of MODY in patients with young-onset diabetes. Diabetologia. 2012;55:1265–72. CrossRefPubMedPubMedCentral
Bellanné-Chantelot C, Carette C, Riveline J, 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;57:503–8. CrossRefPubMed
Steele AM, Shields BM, Shepherd M, et al. Increased all-cause and cardiovascular mortality in monogenic diabetes as a result of mutations in the HNF1A gene. Diabet Med. 2010;27:157–61. CrossRefPubMed
Zucman-Rossi J, Jeannot E, Nhieu JT, et al. Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC. Hepatology. 2006;43(3):515–24. CrossRefPubMed
Wobser H, Bonner C, Nolan JJ, et al. Downregulation of protein kinase B/Akt-1 mediates INS-1 insulinoma cell apoptosis induced by dominant-negative suppression of hepatocyte nuclear factor-1alpha function. Diabetologia. 2006;49:519–26. CrossRefPubMed

Novel clinical evidence in continuous glucose monitoring

Novel clinical evidence in continuous glucose monitoring

How real-world studies complement randomized controlled trials

Jean-Pierre Riveline uses data from real-life continuous glucose monitoring studies to illustrate how these can uncover critical information about clinical outcomes that are hard to assess in randomized controlled trials.

This video has been developed through unrestricted educational funding from Abbott Diabetes Care.

Watch the video