Insulin gene mutations as cause of diabetes in children negative for five type 1 diabetes autoantibodies.
OBJECTIVE
Heterozygous, gain-of-function mutations of the insulin gene can cause permanent diabetes with onset ranging from the neonatal period through adulthood. The aim of our study was to screen for the insulin gene in patients who had been clinically classified as type 1 diabetic but who tested negative for type 1 diabetes autoantibodies.


METHODS
We reviewed the clinical records of 326 patients with the diagnosis of type 1 diabetes and identified seven probands who had diabetes in isolation and were negative for five type 1 diabetes autoantibodies. We sequenced the INS gene in these seven patients.


RESULTS
In two patients whose diabetes onset had been at 2 years 10 months of age and at 6 years 8 months of age, respectively, we identified the mutation G(B8)S and a novel mutation in the preproinsulin signal peptide (A(Signal23)S).


CONCLUSIONS
Insulin gene mutations are rare in absolute terms in patients classified as type 1 diabetic (0.6%) but can be identified after a thorough screening of type 1 diabetes autoantibodies.
Bonfanti
Riccardo
R
Department of Pediatrics, San Raffaele Hospital and Scientific Institute, Milan, Italy.
Colombo
Carlo
C
Nocerino
Valentina
V
Massa
Ornella
O
Lampasona
Vito
V
Iafusco
Dario
D
Viscardi
Matteo
M
Chiumello
Giuseppe
G
Meschi
Franco
F
Barbetti
Fabrizio
F
D000293:Adolescent; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D006580:Genetic Carrier Screening; D006801:Humans; D007223:Infant; D007328:Insulin / Q000235:genetics*; D007330:Insulin Antibodies / Q000097:blood; D009154:Mutation; D011498:Protein Precursors / Q000235:genetics; D012189:Retrospective Studies
D001323:Autoantibodies; C096322:ICA512 autoantibody; D007328:Insulin; D007330:Insulin Antibodies; D011498:Protein Precursors; C024211:islet cell antibody; C013737:preproinsulin