Mutations in ATP-Sensitive K+ Channel Genes Cause Transient Neonatal Diabetes and Permanent Diabetes in Childhood or Adulthood

  1. Sarah E. Flanagan1,
  2. Ann-Marie Patch1,
  3. Deborah J.G. Mackay23,
  4. Emma L. Edghill1,
  5. Anna L. Gloyn14,
  6. David Robinson2,
  7. Julian P.H. Shield5,
  8. Karen Temple36,
  9. Sian Ellard1 and
  10. Andrew T. Hattersley1
  1. 1Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, U.K
  2. 2Wessex Regional Genetics Laboratories, Salisbury District Hospital, Salisbury, U.K
  3. 3Division of Human Genetics, Southampton University, Southampton, U.K
  4. 4Diabetes Research Laboratories, Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford, U.K
  5. 5The Royal Hospital for Children, Bristol, U.K
  6. 6Wessex Clinical Genetics Service, National Health Service Trust, Southampton, U.K
  1. Address correspondence and reprint requests to Professor Andrew T. Hattersley, Peninsula Medical School, Barrack Road, Exeter, EX2 5DW, U.K. E-mail: a.t.hattersley{at}


Transient neonatal diabetes mellitus (TNDM) is diagnosed in the first 6 months of life, with remission in infancy or early childhood. For ∼50% of patients, their diabetes will relapse in later life. The majority of cases result from anomalies of the imprinted region on chromosome 6q24, and 14 patients with ATP-sensitive K+ channel (KATP channel) gene mutations have been reported. We determined the 6q24 status in 97 patients with TNDM. In patients in whom no abnormality was identified, the KCNJ11 gene and/or ABCC8 gene, which encode the Kir6.2 and SUR1 subunits of the pancreatic β-cell KATP channel, were sequenced. KATP channel mutations were found in 25 of 97 (26%) TNDM probands (12 KCNJ11 and 13 ABCC8), while 69 of 97 (71%) had chromosome 6q24 abnormalities. The phenotype associated with KCNJ11 and ABCC8 mutations was similar but markedly different from 6q24 patients who had a lower birth weight and who were diagnosed and remitted earlier (all P < 0.001). KATP channel mutations were identified in 26 additional family members, 17 of whom had diabetes. Of 42 diabetic patients, 91% diagnosed before 6 months remitted, but those diagnosed after 6 months had permanent diabetes (P < 0.0001). KATP channel mutations account for 89% of patients with non-6q24 TNDM and result in a discrete clinical subtype that includes biphasic diabetes that can be treated with sulfonylureas. Remitting neonatal diabetes was observed in two of three mutation carriers, and permanent diabetes occurred after 6 months of age in subjects without an initial diagnosis of neonatal diabetes.


  • Published ahead of print at on 19 April 2007. DOI: 10.2337/db07-0043.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted April 6, 2007.
    • Received January 15, 2007.
No Related Web Pages
| Table of Contents