Referenced in: none

Automatically associated channels: Kir1.1 , Kir6.2

Title: Permanent neonatal diabetes due to a novel insulin signal peptide mutation.

Authors: Suhaimi Hussain, Johari Mohd Ali, Muhammad Yazid Jalaludin, Fatimah Harun

Journal, date & volume: Pediatr Diabetes, 2013 Jun , 14, 299-303

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23350652

Abstract
We report a rare case of permanent neonatal diabetes (PND) due to insulin (INS) gene mutation in a 51-month-old girl who presented with hyperglycemia in the neonatal period. Mutational analysis of KCNJ11 and INS was performed and this detected a novel heterozygous c.38T>G (p.Leu13Arg) INS de novo mutation. The non-conservative change substitutes the highly conserved L(13) residue within the hydrophobic core region of the preproinsulin signal peptide. Given the frequent tendency of heterozygous INS mutations to exhibit dominant negative disease pathogenesis, it is likely that the mutant preproinsulin perturbed the non-mutant counterpart progression and processing within the β-cells, and this resulted to a permanent form of congenital diabetes.