title: Molecular basis of neonatal diabetes in Japanese patients.
abstract: BACKGROUND
  Neonatal diabetes mellitus (NDM) is classified clinically into a transient form (TNDM), in which insulin secretion recovers within several months, and a permanent form (PNDM), requiring lifelong medication. However, these conditions are genetically heterogeneous.
  
  
  OBJECTIVE
  Our objective was to evaluate the contribution of the responsible gene and delineate their clinical characteristics.
  
  
  METHODS
  The chromosome 6q24 abnormality and KCNJ11 and ABCC8 mutations were analyzed in 31 Japanese patients (16 with TNDM and 15 with PNDM). Moreover, FOXP3 and IPF1 mutations were analyzed in a patient with immune dysregulation, polyendocrinopathy, enteropathy X-linked syndrome and with pancreatic agenesis, respectively.
  
  
  RESULTS
  A molecular basis for NDM was found in 23 patients: 6q24 in eleven, KCNJ11 in nine, ABCC8 in two, and FOXP3 in one. All the patients with the 6q24 abnormality and two patients with the KCNJ11 mutation proved to be TNDM. Five mutations were novel: two (p.A174G and p.R50G) [corrected] in KCNJ11, two (p.A90V and p.N1122D) in ABCC8, and one (p.P367L) in FOXP3. Comparing the 6q24 abnormality and KCNJ11 mutation, there were some significant clinical differences: the earlier onset of diabetes, the lower frequency of diabetic ketoacidosis at onset, and the higher proportion of the patients with macroglossia at initial presentation in the patients with 6q24 abnormality. In contrast, two patients with the KCNJ11 mutations manifested epilepsy and developmental delay.
  
  
  CONCLUSIONS
  Both the 6q24 abnormality and KCNJ11 mutation are major causes of NDM in Japanese patients. Clinical differences between them could provide important insight into the decision of which gene to analyze in affected patients first.
authors.affiliation: Department of Pediatrics, Asahikawa Medical College, 2-1-1-1 Midorigaoka Higashi, Asahikawa 078-8510, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Suzuki
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Makita
authors.forename: Tokuo
authors.initials: T
authors.lastname: Mukai
authors.forename: Kumihiro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Osamu
authors.initials: O
authors.lastname: Ueda
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujieda
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D001724:Birth Weight; D002896:Chromosomes, Human, Pair 6; D002658:Developmental Disabilities / Q000208:ethnology / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000208:ethnology* / Q000235:genetics*; D004827:Epilepsy / Q000208:ethnology / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000208:ethnology* / Q000235:genetics; D008260:Macroglossia / Q000208:ethnology / Q000235:genetics; D008297:Male; D009154:Mutation; D015221:Potassium Channels / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D015995:Prevalence; D011955:Receptors, Drug / Q000235:genetics; D020127:Recovery of Function; D064233:Sulfonylurea Receptors; D015534:Trans-Activators / Q000235:genetics; D000099161:Kcnj11 Channel
chemical_list: D018528:ATP-Binding Cassette Transporters; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D015534:Trans-Activators; D000099161:Kcnj11 Channel; C418974:FOXP3 protein, human; C084010:pancreatic and duodenal homeobox 1 protein