|
 |
|
|||||||
|
|||||||||
Diabetes 52:2403-2410, 2003
© 2003 by the American Diabetes Association, Inc.
Clinical and Molecular Characterization of a Dominant Form of Congenital Hyperinsulinism Caused by a Mutation in the High-Affinity Sulfonylurea Receptor
1 Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
2 Division of Endocrinology and Department of Pathology, the Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
3 Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
4 Department of Molecular and Cellular Biology, Division of Endocrinology, Baylor College of Medicine, Houston, Texas
5 Department of Medicine, Division of Endocrinology, Baylor College of Medicine, Houston, Texas
Recessive mutations of sulfonylurea receptor 1 (SUR1) and potassium inward rectifier 6.2 (Kir6.2), the two adjacent genes on chromosome 11p that comprise the ß-cell plasma membrane ATP-sensitive K+ (KATP) channels, are responsible for the most common form of congenital hyperinsulinism in children. The present study was undertaken to identify the genetic defect in a family with dominantly inherited hyperinsulinism affecting five individuals in three generations. Clinical tests were carried out in three of the patients using acute insulin responses (AIRs) to intravenous stimuli to localize the site of defect in insulin regulation. The affected individuals showed abnormal positive calcium AIR, normal negative leucine AIR, subnormal positive glucose AIR, and impaired tolbutamide AIR. This AIR pattern suggested a KATP channel defect because it resembled that seen in children with recessive hyperinsulinism due to two common SUR1 mutations, g3992-9a and delPhe1388. Genetic linkage to the KATP locus was established using intragenic polymorphisms. Mutation analysis identified a novel trinucleotide deletion in SUR1 exon 34 that results in the loss of serine 1387. Studies of delSer1387 in COSm6 cells confirmed that the expressed mutant protein assembles with Kir6.2 and trafficks to the plasma membrane, but it had no 86Rb efflux ion transport activity. These results indicate that hyperinsulinism in this family is caused by a SUR1 mutation that is expressed dominantly rather than recessively.
Address correspondencereprint requests to Charles A. Stanley, MD, Division of Endocrinology, Children’s Hospital of Philadelphia, 34th St. & Civic Center Boulevard, Philadelphia, PA 19104. E-mail stanleyc{at}email.chop.edu
CiteULike 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Abdulhadi-Atwan, J. D. Bushman, S. Tornovsky-Babaey, A. Perry, A. Abu-Libdeh, B. Glaser, S.-L. Shyng, and D. H. Zangen Novel De Novo Mutation in Sulfonylurea Receptor 1 Presenting as Hyperinsulinism in Infancy Followed by Overt Diabetes in Early Adolescence Diabetes, July 1, 2008; 57(7): 1935 - 1940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shi, Z. Wu, N. Cui, W. Shi, Y. Yang, X. Zhang, A. Rojas, B. T. Ha, and C. Jiang PKA phosphorylation of SUR2B subunit underscores vascular KATP channel activation by beta-adrenergic receptors Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1205 - R1214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Thamotharan, M. Garg, S. Oak, L. M. Rogers, G. Pan, F. Sangiorgi, P. W. N. Lee, and S. U. Devaskar Transgenerational inheritance of the insulin-resistant phenotype in embryo-transferred intrauterine growth-restricted adult female rat offspring Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1270 - E1279. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Li, A. Matter, A. Kelly, T. J. Petty, H. Najafi, C. MacMullen, Y. Daikhin, I. Nissim, A. Lazarow, J. Kwagh, et al. Effects of a GTP-insensitive Mutation of Glutamate Dehydrogenase on Insulin Secretion in Transgenic Mice J. Biol. Chem., June 2, 2006; 281(22): 15064 - 15072. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Remedi, Joseph. C. Koster, K. Markova, S. Seino, T. Miki, B. L. Patton, M. L. McDaniel, and C. G. Nichols Diet-Induced Glucose Intolerance in Mice With Decreased {beta}-Cell ATP-Sensitive K+ Channels Diabetes, December 1, 2004; 53(12): 3159 - 3167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. N. Magge, S.-L. Shyng, C. MacMullen, L. Steinkrauss, A. Ganguly, L. E. L. Katz, and C. A. Stanley Familial Leucine-Sensitive Hypoglycemia of Infancy Due to a Dominant Mutation of the {beta}-Cell Sulfonylurea Receptor J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4450 - 4456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Fourtner and C. A. Stanley Genetic and Nongenetic Forms of Hyperinsulinism in Neonates NeoReviews, September 1, 2004; 5(9): e370 - e376. [Full Text] [PDF]
|
|
|
|
|
|
C. Li, C. Buettger, J. Kwagh, A. Matter, Y. Daikhin, I. B. Nissim, H. W. Collins, M. Yudkoff, C. A. Stanley, and F. M. Matschinsky A Signaling Role of Glutamine in Insulin Secretion J. Biol. Chem., April 2, 2004; 279(14): 13393 - 13401. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Ashcroft and P. Rorsman Type 2 diabetes mellitus: not quite exciting enough? Hum. Mol. Genet., April 1, 2004; 13(suppl_1): R21 - R31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Crane and L. Aguilar-Bryan Assembly, Maturation, and Turnover of KATP Channel Subunits J. Biol. Chem., March 5, 2004; 279(10): 9080 - 9090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Stanley, P. S. Thornton, A. Ganguly, C. MacMullen, P. Underwood, P. Bhatia, L. Steinkrauss, L. Wanner, R. Kaye, E. Ruchelli, et al. Preoperative Evaluation of Infants with Focal or Diffuse Congenital Hyperinsulinism by Intravenous Acute Insulin Response Tests and Selective Pancreatic Arterial Calcium Stimulation J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 288 - 296. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Diabetes | Diabetes Care | Clinical Diabetes | Diabetes Spectrum |