title: Gain-of-function mutations in the K(ATP) channel (KCNJ11) impair coordinated hand-eye tracking.
abstract: BACKGROUND
  Gain-of-function mutations in the ATP-sensitive potassium channel can cause permanent neonatal diabetes mellitus (PNDM) or neonatal diabetes accompanied by a constellation of neurological symptoms (iDEND syndrome). Studies of a mouse model of iDEND syndrome revealed that cerebellar Purkinje cell electrical activity was impaired and that the mice exhibited poor motor coordination. In this study, we probed the hand-eye coordination of PNDM and iDEND patients using visual tracking tasks to see if poor motor coordination is also a feature of the human disease.
  
  
  METHODS
  Control participants (n = 14), patients with iDEND syndrome (n = 6 or 7), and patients with PNDM (n = 7) completed three computer-based tasks in which a moving target was tracked with a joystick-controlled cursor. Patients with PNDM and iDEND were being treated with sulphonylurea drugs at the time of testing.
  
  
  RESULTS
  No differences were seen between PNDM patients and controls. Patients with iDEND syndrome were significantly less accurate than controls in two of the three tasks. The greatest differences were seen when iDEND patients tracked blanked targets, i.e. when predictive tracking was required. In this task, iDEND patients incurred more discrepancy errors (p = 0.009) and more velocity errors (p= 0.009) than controls.
  
  
  CONCLUSIONS
  These results identify impaired hand-eye coordination as a new clinical feature of iDEND. The aetiology of this feature is likely to involve cerebellar dysfunction. The data further suggest that sulphonylurea doses that control the diabetes of these patients may be insufficient to fully correct their neurological symptoms.
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, Oxfordshire, United Kingdom.
authors.forename: James S
authors.initials: JS
authors.lastname: McTaggart
authors.forename: Ned
authors.initials: N
authors.lastname: Jenkinson
authors.forename: John-Stuart
authors.initials: JS
authors.lastname: Brittain
authors.forename: Siri A W
authors.initials: SA
authors.lastname: Greeley
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: Frances M
authors.initials: FM
authors.lastname: Ashcroft
mesh_terms: D005133:Eye Movements; D006225:Hand; D006801:Humans; D009154:Mutation; D009422:Nervous System Diseases / Q000235:genetics* / Q000503:physiopathology*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics* / Q000378:metabolism*; D011597:Psychomotor Performance; D013577:Syndrome; D000099161:Kcnj11 Channel
chemical_list: D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel