title: Activating mutations in the KCNJ11 gene encoding the ATP-sensitive K+ channel subunit Kir6.2 are rare in clinically defined type 1 diabetes diagnosed before 2 years.
abstract: We have recently shown that permanent neonatal diabetes can be caused by activating mutations in KCNJ11 that encode the Kir6.2 subunit of the beta-cell ATP-sensitive K(+) channel. Some of these patients were diagnosed after 3 months of age and presented with ketoacidosis and marked hyperglycemia, which could have been diagnosed as type 1 diabetes. We hypothesized that KCNJ11 mutations could present clinically as type 1 diabetes. We screened the KCNJ11 gene for mutations in 77 U.K. type 1 diabetic subjects diagnosed under the age of 2 years. One patient was found to be heterozygous for the missense mutation R201C. She had low birth weight, was diagnosed at 5 weeks, and did not have a high risk predisposing HLA genotype. A novel variant, R176C, was identified in one diabetic subject but did not cosegregate with diabetes within the family. In conclusion, we have shown that heterozygous activating mutations in the KCNJ11 gene are a rare cause of clinically defined type 1 diabetes diagnosed before 2 years. Although activating KCNJ11 mutations are rare in patients diagnosed with type 1 diabetes, the identification of a KCNJ11 mutation may have important treatment implications.
authors.affiliation: Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, Exeter EX2 5AX, UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Edghill
authors.forename: Anna L
authors.initials: AL
authors.lastname: Gloyn
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Gillespie
authors.forename: A Paul
authors.initials: AP
authors.lastname: Lambert
authors.forename: Neil T
authors.initials: NT
authors.lastname: Raymond
authors.forename: Peter G
authors.initials: PG
authors.lastname: Swift
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Edwin A M
authors.initials: EA
authors.lastname: Gale
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D000099161:Kcnj11 Channel
chemical_list: D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel