Inactivation of the first nucleotide-binding fold of the sulfonylurea receptor, and familial persistent hyperinsulinemic hypoglycemia of infancy

Am J Hum Genet. 1996 Sep;59(3):510-8.

Abstract

Familial persistent hyperinsulinemic hypoglycemia of infancy is a disorder of glucose homeostasis and is characterized by unregulated insulin secretion and profound hypoglycemia. Loss-of-function mutations in the second nucleotide-binding fold of the sulfonylurea receptor, a subunit of the pancreatic-islet beta-cell ATP-dependent potassium channel, has been demonstrated to be causative for persistent hyperinsulinemic hypoglycemia of infancy. We now describe three additional mutations in the first nucleotide-binding fold of the sulfonylurea-receptor gene. One point mutation disrupts the highly conserved Walker A motif of the first nucleotide-binding-fold region. The other two mutations occur in noncoding sequences required for RNA processing and are predicted to disrupt the normal splicing pathway of the sulfonylurea-receptor mRNA precursor. These data suggest that both nucleotide-binding-fold regions of the sulfonylurea receptor are required for normal regulation of beta-cell ATP-dependent potassium channel activity and insulin secretion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP-Binding Cassette Transporters*
  • Amino Acid Sequence
  • Base Sequence
  • Child
  • DNA, Complementary / genetics
  • Humans
  • Hyperinsulinism / genetics*
  • Hypoglycemia / genetics*
  • Infant
  • Molecular Sequence Data
  • Nucleotides / metabolism
  • Pancreas
  • Point Mutation / genetics*
  • Potassium Channels / chemistry
  • Potassium Channels / genetics*
  • Potassium Channels, Inwardly Rectifying*
  • RNA Processing, Post-Transcriptional / genetics
  • Receptors, Drug / chemistry
  • Receptors, Drug / genetics*
  • Sequence Homology, Amino Acid
  • Sulfonylurea Compounds*
  • Sulfonylurea Receptors

Substances

  • ATP-Binding Cassette Transporters
  • DNA, Complementary
  • Nucleotides
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Compounds
  • Sulfonylurea Receptors

Associated data

  • GENBANK/U63421
  • GENBANK/U63422
  • GENBANK/U63423
  • GENBANK/U63424
  • GENBANK/U63425
  • GENBANK/U63426
  • GENBANK/U63427
  • GENBANK/U63428
  • GENBANK/U63429
  • GENBANK/U63430
  • GENBANK/U63431
  • GENBANK/U63432
  • GENBANK/U63433
  • GENBANK/U63434
  • GENBANK/U63435
  • GENBANK/U63436
  • GENBANK/U63437
  • GENBANK/U63438
  • GENBANK/U63439
  • GENBANK/U63440
  • GENBANK/U63441
  • GENBANK/U63442
  • GENBANK/U63443
  • GENBANK/U63444
  • GENBANK/U63445
  • GENBANK/U63446
  • GENBANK/U63447
  • GENBANK/U63448
  • GENBANK/U63449
  • GENBANK/U63450