Insulin gene mutations as cause of diabetes in children negative for five type 1 diabetes autoantibodies.
- Riccardo Bonfanti, MD1,
- Carlo Colombo, Bs2,
- Valentina Nocerino, Bs3,
- Ornella Massa, PhD2,
- Vito Lampasona, PhD4,
- Dario Iafusco, MD5,
- Matteo Viscardi, MD1,
- Giuseppe Chiumello, MD1,
- Franco Meschi, MD1 and
- Fabrizio Barbetti, MD, PhD (mody.2{at}libero.it)2,3,6
- 1 Department of Pediatrics, Scientific Institute H San Raffaele, Milan, Italy
- 2 Laboratory of Molecular Endocrinology, Bambino Gesù Pediatric Hospital, IRCCS, Rome, Italy
- 3 Laboratory of Molecular Endocrinology and Metabolism, S Raffaele Biomedical Park Foundation, Rome, Italy
- 4 Diagnostica e Ricerca H San Raffaele and Scientific Institute H San Raffaele, Milan, Italy
- 5 2nd University of Naples, Naples, Italy
- 6 Department of Internal Medicine, University of Tor Vergata, Rome, Italy
Abstract
Objective. Heterozygous, gain-of-function mutations of the insulin gene can cause permanent diabetes mellitus with onset ranging from the neonatal period through adulthood. Aim of our study was to screen the insulin gene in patients clinically classified as T1D, but negative to the search of T1D autoantibodies.
Research design and methods. We reviewed the clinical records of 326 patients with the diagnosis of T1D and identified 7 probands who had diabetes in isolation and were negative for the search of five T1D autoantibodies. We sequenced the INS gene in these 7.
Results. In 2 patients with diabetes onset at 2 y, 10 m and 6 y, 8 m, we identified the mutation GB8S and a novel mutation in the pre(pro)insulin signal peptide (ASignal23S).
Conclusion. Insulin gene mutations are rare in absolute terms in patients classified as T1D (0.6%) but can be identified after a thorough screening of T1D autoantibodies.
Footnotes
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- Received April 27, 2008.
- Accepted September 26, 2008.
- Copyright © American Diabetes Association
