title: Identification of INS and KCNJ11 gene mutations in type 1B diabetes in Japanese children with onset of diabetes before 5 years of age.
abstract: BACKGROUND
  The etiology of type 1 diabetes (T1D) is heterogeneous and is according to presence or absence of pancreatic autoantibodies divided into two subtypes: type 1A (autoimmune-mediated) and type 1B (non-autoimmune-mediated). Although several genes have been linked to type 1A diabetes, the genetic cause of type 1B diabetes in Japanese individuals is far from understood.
  
  
  OBJECTIVE
  The aim of this study was to test for monogenic forms of diabetes in auto antibody-negative Japanese children with T1D.
  
  
  METHODS
  Thirty four (19 males and 15 female) unrelated Japanese children with glutamate decarboxylase (GAD) 65 antibodies and/or IA-2A-negative T1D and diabetes diagnosed at < 5 yr of age were recruited from 17 unrelated hospitals participating in the Japanese Study Group of Insulin Therapy for children and adolescent diabetes (JSGIT). We screened the INS gene and the KCNJ11 gene which encode the ATP-sensitive potassium cannel by direct sequencing in 34 Japanese children with T1D.
  
  
  RESULTS
  We identified three novel (C31Y, C96R, and C109F) mutations and one previously reported mutation (R89C) in the INS gene in five children, in addition to one mutation in the KCNJ11 gene (H46R) in one child. These mutations are most likely pathogenic and therefore the cause of diabetes in carriers.
  
  
  CONCLUSIONS
  Our results suggest that monogenic forms of diabetes, particularly INS gene mutations, can be detected in Japanese patients classified with type 1B. Mutation screening, at least of the INS gene, is recommended for Japanese patients diagnosed as autoantibody negative at <5 yr of age.
authors.affiliation: Laboratory for Pediatrics Genome Medicine, Department of Clinical Research, Kagawa National Children's Hospital, Zentsuji, Kagawa, 765-8501, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Moritani
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yokota
authors.forename: Kohji
authors.initials: K
authors.lastname: Tsubouchi
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Takaya
authors.forename: Koji
authors.initials: K
authors.lastname: Takemoto
authors.forename: Kanshi
authors.initials: K
authors.lastname: Minamitani
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Urakami
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kawamura
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kikuchi
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Itakura
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Sugihara
authors.forename: Shin
authors.initials: S
authors.lastname: Amemiya
mesh_terms: D044466:Asian People / Q000235:genetics; D001323:Autoantibodies / Q000235:genetics; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D006801:Humans; D007328:Insulin / Q000235:genetics*; D007564:Japan; D008297:Male; D010375:Pedigree; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D000099161:Kcnj11 Channel
chemical_list: D001323:Autoantibodies; D007328:Insulin; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel