Diabetes, Vol 49, Issue 9 1597-1600, Copyright © 2000 by American Diabetes Association

ARTICLES

Nonsense mutation of islet-1 gene (Q310X) found in a type 2 diabetic patient with a strong family history

H Shimomura, T Sanke, T Hanabusa, K Tsunoda, H Furuta and K Nanjo
First Department of Medicine, Wakayama University of Medical Science, Japan.

Islet-1 (Isl-1) is one of the transcription factors that play an important role for the formation of the islet cells. We scanned the Isl-1 gene in 77 Japanese type 2 diabetic patients with a family history and found a heterozygous nonsense mutation (Q310X) in 1 diabetic patient. The mutation was not found in 180 nondiabetic subjects. This mutation is located in the putative transactivation domain and deletes 40 amino acids of the COOH-terminal lesion. The Q310X mutant exhibited a 50% reduction in activity compared with the wild-type when tested for stimulation of transcription of a human amylin promoter-linked luciferase reporter gene in betaTC3 cells. The patient was a 49-year-old nonobese man who was diagnosed as having type 2 diabetes at 32 years of age and has been treated with sulfonylureas. The mutation was found in his mother, who has type 2 diabetes, and in his 14-year-old daughter, who has normal glucose tolerance but a relatively low insulin response. This is the first reported finding of Isl-1 gene mutation in type 2 diabetes. Although Isl-1 is not a common predisposing gene for Japanese type 2 diabetes, the mutation in this gene may be a rare cause of diabetes in isolated families.
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