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Licensed Unlicensed Requires Authentication Published by De Gruyter December 9, 2016

An analysis of the sequence of the BAD gene among patients with maturity-onset diabetes of the young (MODY)

Karolina Antosik , Piotr Gnyś , Przemysława Jarosz-Chobot , Małgorzata Myśliwiec , Agnieszka Szadkowska , Maciej Małecki , Wojciech Młynarski and Maciej Borowiec EMAIL logo



Monogenic diabetes is a rare disease caused by single gene mutations. Maturity onset diabetes of the young (MODY) is one of the major forms of monogenic diabetes recognised in the paediatric population. To date, 13 genes have been related to MODY development. The aim of the study was to analyse the sequence of the BCL2-associated agonist of cell death (BAD) gene in patients with clinical suspicion of GCK-MODY, but who were negative for glucokinase (GCK) gene mutations.


A group of 122 diabetic patients were recruited from the “Polish Registry for Paediatric and Adolescent Diabetes – nationwide genetic screening for monogenic diabetes” project. The molecular testing was performed by Sanger sequencing.


A total of 10 sequence variants of the BAD gene were identified in 122 analysed diabetic patients.


Among the analysed patients suspected of MODY, one possible pathogenic variant was identified in one patient; however, further confirmation is required for a certain identification.

Corresponding author: Maciej Borowiec, PhD, Department of Clinical Genetics, Medical University of Lodz, Pomorska 251, 92-213 Lodz, Poland, Phone: +48 42 272 57 67


This study was supported by funds from the National Science Centre, project no. 2011/01/N/NZ5/02758.

  1. Author contributions: All the authors have accepted responsibility for the entire content of the submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


1. Tattersall RB, Fajans SS. A difference between the inheritance of classical juvenile-onset and maturity-onset type diabetes of young people. Diabetes 1975;24:44–53.10.2337/diab.24.1.44Search in Google Scholar PubMed

2. Siddiqui K, Musambil M, Nazir N. Maturity onset diabetes of the young (MODY)-History, first case reports and recent advances. Gene 2015;555:66–71.10.1016/j.gene.2014.09.062Search in Google Scholar PubMed

3. Bowman P, Flanagan SE, Edghill EL, Damhuis A, Shepherd MH, et al. Heterozygous ABCC8 mutations are a cause of MODY. Diabetologia 2012;55:123–7.10.1007/s00125-011-2319-xSearch in Google Scholar PubMed

4. Bonnefond A, Philippe J, Durand E, Dechaume A, Huyvaert M, et al. Whole-Exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene. PLoS One 2012;7:1–8.10.1371/journal.pone.0037423Search in Google Scholar PubMed PubMed Central

5. Osbak KK, Colclough K, Saint-Martin C, Beer NL, Bellanne-Chantelot 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;30:1512–6.10.1002/humu.21110Search in Google Scholar PubMed

6. Agius L. Glucokinase and molecular aspects of liver glycogen metabolism. Biochem J 2008;414:1–18.10.1042/BJ20080595Search in Google Scholar PubMed

7. Baltrusch S, Lenzen S, Okar DA, Lange AJ, Tiedge M. Characterization of glucokinase-binding protein epitopes by a phage-displayed peptide library – identification of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase as a novel interaction partner. J Biol Chem 2001;276:43915–23.10.1074/jbc.M105470200Search in Google Scholar PubMed

8. Danial NN, Gramm CF, Scorrano L, Zhang CY, Krauss S, et al. BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature 2003;424:952–6.10.1038/nature01825Search in Google Scholar PubMed

9. Danial NN, Walensky LD, Zhang CY, Choi CS, Fisher JK, et al. Dual role of proapoptotic BAD in insulin secretion and beta cell survival. Nat Med 2008;14:144–53.10.1038/nm1717Search in Google Scholar PubMed PubMed Central

10. Danial NN. BCL-2 family proteins: Critical checkpoints of apoptotic cell death. Clin Cancer Res 2007;13:7254–63.10.1158/1078-0432.CCR-07-1598Search in Google Scholar PubMed

11. Borowiec M, Antosik K, Fendler W, Deja G, Jarosz-Chobot P, et al. Novel glucokinase mutations in patients with monogenic diabetes – clinical outline of GCK-MD and potential for founder effect in Slavic population. Clin Genet 2012;81:278–83.10.1111/j.1399-0004.2011.01656.xSearch in Google Scholar PubMed

12. Danial NN. BAD: undertaker by night, candyman by day. Oncogene 2008;27:S53–70.10.1038/onc.2009.44Search in Google Scholar PubMed

13. Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V, et al. Proapoptotic BAX and BAK: A requisite gateway to mitochondrial dysfunction and death. Science 2001;292:727–30.10.1126/science.1059108Search in Google Scholar PubMed PubMed Central

14. Postic C, Shiota M, Niswender KD, Jetton TL, Chen YJ, et al. Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic beta cell-specific gene knock-outs using Cre recombinase. J Biol Chem 1999;274:305–15.10.1074/jbc.274.1.305Search in Google Scholar PubMed

15. Philipson LH, Roe MW. When BAD is good for beta cells. Cell Metab 2008;7:280–1.10.1016/j.cmet.2008.03.009Search in Google Scholar PubMed

Received: 2016-6-14
Accepted: 2016-11-3
Published Online: 2016-12-9
Published in Print: 2017-1-1

©2017 Walter de Gruyter GmbH, Berlin/Boston

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