Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood

Flanagan, Sarah E., Patch, Ann-Marie, Mackay, Deborah J. G., Edghill, Emma L., Gloyn, Anna L., Robinson, David, Shield, Julian P. H., Temple, Karen, Ellard, Sian and Hattersley, Andrew T. (2007) Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood. Diabetes, 56 7: 1930-1937. doi:10.2337/db07-0043


Author Flanagan, Sarah E.
Patch, Ann-Marie
Mackay, Deborah J. G.
Edghill, Emma L.
Gloyn, Anna L.
Robinson, David
Shield, Julian P. H.
Temple, Karen
Ellard, Sian
Hattersley, Andrew T.
Title Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood
Formatted title
Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood
Journal name Diabetes   Check publisher's open access policy
ISSN 0012-1797
1939-327X
Publication date 2007-07-01
Sub-type Article (original research)
DOI 10.2337/db07-0043
Open Access Status Not Open Access
Volume 56
Issue 7
Start page 1930
End page 1937
Total pages 8
Place of publication Alexandria, VA, U.S.A.
Publisher American Diabetes Association
Language eng
Formatted abstract
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.
Keyword KATP channel
ATP-sensitive K+ channel
PNDM
Permanent neonatal diabetes mellitus
TNDM
Transient neonatal diabetes mellitus
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Erratum: Diabetes Volume: 57 Issue: 2 Pages: 523-523 Published: February 2008

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
Institute for Molecular Bioscience - Publications
 
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Created: Thu, 05 May 2011, 22:16:41 EST by Susan Allen on behalf of Institute for Molecular Bioscience