Gain-of-function mutations of KCNJ11 can cause permanent neonatal diabetes 
mellitus, but only rarely after 6 months of age. Specific uncommon mutations 
KCNJ11give rise to a syndrome defined as developmental delay, epilepsy, and 
neonatal diabetes (DEND), or - more frequently - to a milder sub-type lacking 
epilepsy, denoted as intermediate-DEND (iDEND). Our aim was to consider a 
possible monogenic etiology in a 12-yr-old boy with early onset diabetes and 
mild neurological features. We studied a subject diagnosed with diabetes at 
21 months of age, and negative to type 1 diabetes autoantibodies testing. He had 
learning difficulties during primary school, and a single episode of seizures at 
the age of 10 yr. We performed direct DNA sequencing of the KCNJ11 gene with 
subsequent functional study of mutated channels in COSm6 cells. The patient's 
clinical response to oral glyburide (Glyb) was assessed. Motor coordination was 
evaluated before and after 6 and 12 months of Glyb therapy. Sequencing of the 
KCNJ11 gene detected the novel, spontaneous mutation S225T, combined with 
deletion of amino acids 226-232. In vitro studies revealed that the mutation 
results in a K(ATP) channel with reduced sensitivity to the inhibitory action of 
ATP. Glyb improved diabetes control (hemoglobin A1c on insulin: 
52 mmol/mol/6.9%; on Glyb: 36 mmol/mol/5.4%) and also performance on motor 
coordination tests that were impaired before the switch of therapy. We conclude 
that KCNJ11/S225T, del226-232 mutation caused a mild iDEND form in our patient. 
KCNJ11 should be considered as the etiology of diabetes even beyond the neonatal 
period if present in combination with negative autoantibody testing and even 
mild neurological symptoms.