Permanent neonatal diabetes due to a novel insulin signal peptide mutation.
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.
Department of Paediatrics, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia. grinfin06@yahoo.com
Suhaimi
S
Hussain
Johari
J
Mohd Ali
Muhammad Yazid
MY
Jalaludin
Fatimah
F
Harun
D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000151:congenital* / Q000235:genetics; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000235:genetics*; D007328:Insulin / Q000235:genetics*; D007336:Insulin, Isophane / Q000008:administration & dosage; D061386:Insulin, Regular, Human / Q000008:administration & dosage; D000068880:Isophane Insulin, Human; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics; D021382:Protein Sorting Signals / Q000235:genetics; D000099161:Kcnj11 Channel
D007328:Insulin; D007336:Insulin, Isophane; D061386:Insulin, Regular, Human; D000068880:Isophane Insulin, Human; D024661:Potassium Channels, Inwardly Rectifying; D011498:Protein Precursors; D021382:Protein Sorting Signals; D000099161:Kcnj11 Channel; C013737:preproinsulin