title: Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy.
abstract: Familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI), an autosomal recessive disorder characterized by unregulated insulin secretion, is linked to chromosome 11p14-15.1. The newly cloned high-affinity sulfonylurea receptor (SUR) gene, a regulator of insulin secretion, was mapped to 11p15.1 by means of fluorescence in situ hybridization. Two separate SUR gene splice site mutations, which segregated with disease phenotype, were identified in affected individuals from nine different families. Both mutations resulted in aberrant processing of the RNA sequence and disruption of the putative second nucleotide binding domain of the SUR protein. Abnormal insulin secretion in PHHI appears to be caused by mutations in the SUR gene.
authors.affiliation: Department of Medical Specialties, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Thomas
authors.forename: G J
authors.initials: GJ
authors.lastname: Cote
authors.forename: N
authors.initials: N
authors.lastname: Wohllk
authors.forename: B
authors.initials: B
authors.lastname: Haddad
authors.forename: P M
authors.initials: PM
authors.lastname: Mathew
authors.forename: W
authors.initials: W
authors.lastname: Rabl
authors.forename: L
authors.initials: L
authors.lastname: Aguilar-Bryan
authors.forename: R F
authors.initials: RF
authors.lastname: Gagel
authors.forename: J
authors.initials: J
authors.lastname: Bryan
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D005838:Genotype; D006801:Humans; D006946:Hyperinsulinism / Q000235:genetics*; D007003:Hypoglycemia / Q000235:genetics*; D007223:Infant; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008969:Molecular Sequence Data; D009154:Mutation; D010182:Pancreatic Diseases / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying; D012326:RNA Splicing; D011955:Receptors, Drug / Q000737:chemistry / Q000235:genetics*; D013453:Sulfonylurea Compounds / Q000378:metabolism; D064233:Sulfonylurea Receptors
chemical_list: D018528:ATP-Binding Cassette Transporters; D018076:DNA, Complementary; D007328:Insulin; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors