Insulin Gene Mutations as Cause of Diabetes in Children Negative for Five Type 1 Diabetes Autoantibodies
- Riccardo Bonfanti, MD1,
- Carlo Colombo2,
- Valentina Nocerino3,
- Ornella Massa, PHD2,
- Vito Lampasona, PHD4,
- Dario Iafusco, MD5,
- Matteo Viscardi, MD1,
- Giuseppe Chiumello, MD1,
- Franco Meschi, MD1 and
- Fabrizio Barbetti, MD, PHD236
- 1Department of Pediatrics, San Raffaele Hospital and Scientific Institute, Milan, Italy
- 2Laboratory of Molecular Endocrinology, Bambino Gesù Pediatric Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy
- 3Laboratory of Molecular Endocrinology and Metabolism, San Raffaele Biomedical Park Foundation, Rome, Italy
- 4Laboraf Diagnostica e Ricerca San Raffaele S.p.A., Milan, Italy
- 5Second University of Naples, Naples, Italy
- 6Department of Internal Medicine, University of Rome–Tor Vergata, Rome, Italy
- Corresponding author: Fabrizio Barbetti, mody.2{at}libero.it
Abstract
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.
RESEARCH DESIGN AND 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 GB8S and a novel mutation in the preproinsulin signal peptide (ASignal23S).
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.
Footnotes
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Published ahead of print at http://care.diabetesjournals.org on 7 October 2008.
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- Accepted September 26, 2008.
- Received April 27, 2008.
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