Novel glucokinase mutations in patients with monogenic diabetes – clinical outline of GCK-MD and potential for founder effect in Slavic population
Article first published online: 18 MAR 2011
© 2011 John Wiley & Sons A/S
Volume 81, Issue 3, pages 278–283, March 2012
How to Cite
Borowiec, M., Antosik, K., Fendler, W., Deja, G., Jarosz-Chobot, P., Mysliwiec, M., Zmyslowska, A., Malecki, M., Szadkowska, A. and Mlynarski, W. (2012), Novel glucokinase mutations in patients with monogenic diabetes – clinical outline of GCK-MD and potential for founder effect in Slavic population. Clinical Genetics, 81: 278–283. doi: 10.1111/j.1399-0004.2011.01656.x
- Issue published online: 31 JAN 2012
- Article first published online: 18 MAR 2011
- Accepted manuscript online: 23 FEB 2011 09:12AM EST
- Received 6 September 2010, revised and accepted for publication 21 February 2011
- DNA sequencing;
- founder effect;
- monogenic diabetes;
- neonatal diabetes
Borowiec M, Antosik K, Fendler W, Deja G, Jarosz-Chobot P, Mysliwiec M, Zmyslowska A, Malecki M, Szadkowska A, Mlynarski W. Novel glucokinase mutations in patients with monogenic diabetes – clinical outline of GCK-MD and potential for founder effect in Slavic population.
Glucokinase (GCK) gene mutations are the causative factor of GCK-MD (monogenic diabetes) characterized by a mild clinical phenotype and potential for insulin withdrawal. This study presents the results of a nationwide genetic screening for GCK-MD performed in Poland. A group of 194 patients with clinical suspicion of GCK-MD and 17 patients with neonatal diabetes were subjected to GCK sequencing. Patients negative for GCK mutations were subjected to multiplex ligation-dependent probe amplification (MLPA) to detect deletions or insertions. A total of 44 GCK heterozygous mutations were found in 68 probands (35%). Among those, 20 mutations were novel ones: A282fs, D198V, E158X, G246V, G249R, I348N, L165V, L315Q, M115I, N254S, P284fs, Q338P, R377L, R43C, R46S, S212fs, S212P, T255N, V406A and Y214D. No abnormalities were detected in MLPA analysis. Homozygous D278E mutation was found in one patient with neonatal diabetes. The most frequently observed combinations of symptoms typical for GCK-MD were mild diabetes and/or fasting hyperglycaemia (98.3%), positive C-peptide at diagnosis (76%) and dominant mode of inheritance (59%). This study outlines numerous novel mutations of the GCK gene present in white Caucasians of Slavic origin. Thorough clinical assessment of known factors associated with GCK-MD may facilitate patient selection.