title: Nonsense mutation of islet-1 gene (Q310X) found in a type 2 diabetic patient with a strong family history.
abstract: 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.
authors.affiliation: First Department of Medicine, Wakayama University of Medical Science, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Shimomura
authors.forename: T
authors.initials: T
authors.lastname: Sanke
authors.forename: T
authors.initials: T
authors.lastname: Hanabusa
authors.forename: K
authors.initials: K
authors.lastname: Tsunoda
authors.forename: H
authors.initials: H
authors.lastname: Furuta
authors.forename: K
authors.initials: K
authors.lastname: Nanjo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D000682:Amyloid / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000097:blood; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000378:metabolism; D007564:Japan; D060850:LIM-Homeodomain Proteins; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins; D010375:Pedigree; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014157:Transcription Factors; D014162:Transfection
chemical_list: D000682:Amyloid; D001786:Blood Glucose; D018398:Homeodomain Proteins; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1