HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Online-Only Appendix All Versions of this Article: db06-1540v1 56/6/1737    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vaxillaire, M. Search for Related Content PubMed PubMed Citation Articles by Vaxillaire, M. Social Bookmarking                What's this?

New ABCC8 mutations in Relapsing Neonatal Diabetes and Clinical Features

¹CNRS, 8090-Institute of Biology, Pasteur Institute, Lille, France
²Faculty of Medicine, René Descartes Paris 5 University, Paris, France
³Genetic Biochemistry, Robert Debré Hospital, Paris, France
⁴Inserm, EMI 0363, Necker Enfants Malades Hospital, Paris, France
⁵Endocrinology and Diabetes Research Group, Hospital de Cruces, Barakaldo, Bizkaia, Spain
⁶Genomic Medicine, Hammersmith Hospital, Imperial College, London, United Kingdom
⁷Department of Pediatric Endocrinology, Necker Enfants Malades Hospital, Paris, France

Correspondence: martine.vaxillaire{at}good.ibl.fr

Key Words: ABCC8 • ATP-sensitive potassium channel • Diabetes • Genetics • Neonatal diabetes • SUR1

Activating mutations in the ABCC8 gene that encodes the SUR1 regulatory subunit of the pancreatic islet ATP-sensitive potassium (K_ATP) channel cause both permanent and transient neonatal diabetes mellitus (NDM). Recently, we have described the novel mechanism where basal Mg-nucleotide-dependent stimulatory action of SUR1 on the K_IR6.2 pore is increased. In our present study, we identified six new heterozygous ABCC8 mutations mainly in patients presenting the transient form of NDM (6/8), with a median duration of initial insulin therapy of 17 months (range 0.5-38). Most of these mutations map to key functional domains of SUR1. Whereas K_IR6.2 mutations are a common cause of permanent NDM and in a few cases associate with the DEND syndrome, SUR1 mutations are more frequent in transient (52%) compared to permanent (14%) NDM cases screened for ABCC8 in our series. Although ketoacidosis is frequent at presentation, SUR1 mutations associate mainly with transient hyperglycemia with possible recurrence later in life. Half of the SUR1-NDM patients presented with de novo mutations. In some of the cases that are familial, diabetes is not always present in the adult carriers of SUR1 mutations supporting variability in their clinical expressivity that remains to be fully explained.

CiteULike

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				M. Polak, A. Dechaume, H. Cave, R. Nimri, H. Crosnier, V. Sulmont, M. de Kerdanet, R. Scharfmann, Y. Lebenthal, P. Froguel, et al. Heterozygous Missense Mutations in the Insulin Gene Are Linked to Permanent Diabetes Appearing in the Neonatal Period or in Early Infancy: A Report From the French ND (Neonatal Diabetes) Study Group Diabetes, April 1, 2008; 57(4): 1115 - 1119. [Abstract] [Full Text] [PDF]

				J. P.H. Shield, S. E. Flanagan, D. J. Mackay, L. W. Harries, P. Proks, C. Girard, F. M. Ashcroft, I. K. Temple, and S. Ellard Mosaic Paternal Uniparental Isodisomy and an ABCC8 Gene Mutation in a Patient With Permanent Neonatal Diabetes and Hemihypertrophy Diabetes, January 1, 2008; 57(1): 255 - 258. [Abstract] [Full Text] [PDF]

				M. Polak Neonatal Diabetes Mellitus: Insights for More Common Forms of Diabetes J. Clin. Endocrinol. Metab., October 1, 2007; 92(10): 3774 - 3776. [Full Text] [PDF]