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

Journal Article · Sun Sep 01 00:00:00 EDT 1996 · American Journal of Human Genetics

OSTI ID:478500

Thomas, P M; Wohllk, N; Huang, E ^[1]

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1. Univ. of Texas, Houston, TX (United States); and others

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 sulfortylurea receptor are required for normal regulation of {beta}-cell ATP-dependent potassium channel activity and insulin secretion. 32 refs., 4 figs., 1 tab.

• OSTI ID: 478500
• Journal Information: American Journal of Human Genetics, Vol. 59, Issue 3; Other Information: PBD: Sep 1996
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
PATIENTS
HEREDITARY DISEASES
METABOLIC DISEASES
GLUCOSE
HOMEOSTASIS
INSULIN
SECRETION
PORINS
RECEPTORS
GENE MUTATIONS
SPLICING
GENE REGULATION
GENETIC MAPPING
DNA SEQUENCING
HUMAN CHROMOSOMES
NUCLEOTIDES
CHIMERAS
POTASSIUM
RECESSIVE MUTATIONS
POLYMERASE CHAIN REACTION