title: NIDDM associated with mutation in tyrosine kinase domain of insulin receptor gene.
abstract: A population of 103 patients with non-insulin-dependent diabetes mellitus (NIDDM) was screened for mutations in the tyrosine kinase domain of the insulin receptor gene. Patient genomic DNAs corresponding to exons 17-21 of the insulin receptor gene have been amplified by polymerase chain reaction and analyzed by denaturing gradient gel electrophoresis (DGGE). One patient was identified with an altered pattern of mobility of exon 20 in the DGGE assay. Direct sequence of amplified DNA showed a single nucleotide substitution in the codon 1152 (CGG-- greater than CAG), resulting in the replacement of Arg with Gln. Two bands appeared in the sequence of exon 20 of the insulin receptor (nucleotide position 3584), indicating that this patient was heterozygous for the mutation. Insulin binding to intact erythrocytes from the patient was in the normal range. Although autophosphorylation of the purified insulin receptor also seemed normal, its kinase activity toward the exogenous substrate poly Glu:Tyr (4:1) was undetectable. This mutation may impair insulin receptor kinase and contribute to insulin resistance in this patient.
authors.affiliation: Department of Cellular and Molecular Biology and Pathology, L. Califano, Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Richerche; Naples, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cocozza
authors.forename: A
authors.initials: A
authors.lastname: Porcellini
authors.forename: G
authors.initials: G
authors.lastname: Riccardi
authors.forename: A
authors.initials: A
authors.lastname: Monticelli
authors.forename: G
authors.initials: G
authors.lastname: Condorelli
authors.forename: A
authors.initials: A
authors.lastname: Ferrara
authors.forename: L
authors.initials: L
authors.lastname: Pianese
authors.forename: C
authors.initials: C
authors.lastname: Miele
authors.forename: B
authors.initials: B
authors.lastname: Capaldo
authors.forename: F
authors.initials: F
authors.lastname: Beguinot
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000032:analysis / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D004912:Erythrocytes / Q000648:ultrastructure; D005091:Exons; D005260:Female; D005796:Genes / Q000235:genetics*; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009691:Nucleic Acid Denaturation; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011972:Receptor, Insulin / Q000235:genetics*
chemical_list: D004247:DNA; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin