title: Two mutant alleles of the insulin receptor gene in a patient with extreme insulin resistance.
abstract: Insulin receptor complementary DNA has been cloned from an insulin-resistant patient with leprechaunism whose receptors exhibited multiple abnormalities in insulin binding. The patient is a compound heterozygote, having inherited two different mutant alleles of the insulin receptor gene. One allele contains a missense mutation encoding the substitution of glutamic acid for lysine at position 460 in the alpha subunit of the receptor. The second allele has a nonsense mutation causing premature chain termination after amino acid 671 in the alpha subunit, thereby deleting both the transmembrane and tyrosine kinase domains of the receptor. Interestingly, the father is heterozygous for this nonsense mutation and exhibits a moderate degree of insulin resistance. This raises the possibility that mutations in the insulin receptor gene may account for the insulin resistance in some patients with non-insulin-dependent diabetes mellitus.
authors.affiliation: Biochemistry and Molecular Pathophysiology Section, National Institute of Diabetes, Digestive, and Kidney Disease, Bethesda, MD 20892.
authors.forename: T
authors.initials: T
authors.lastname: Kadowaki
authors.forename: C L
authors.initials: CL
authors.lastname: Bevins
authors.forename: A
authors.initials: A
authors.lastname: Cama
authors.forename: K
authors.initials: K
authors.lastname: Ojamaa
authors.forename: B
authors.initials: B
authors.lastname: Marcus-Samuels
authors.forename: H
authors.initials: H
authors.lastname: Kadowaki
authors.forename: L
authors.initials: L
authors.lastname: Beitz
authors.forename: C
authors.initials: C
authors.lastname: McKeon
authors.forename: S I
authors.initials: SI
authors.lastname: Taylor
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002472:Cell Transformation, Viral; D004247:DNA / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004700:Endocrine System Diseases / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D006130:Growth Disorders / Q000235:genetics; D004854:Herpesvirus 4, Human; D006579:Heterozygote; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D008214:Lymphocytes / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D009154:Mutation; D011972:Receptor, Insulin / Q000235:genetics*; D013577:Syndrome; D014162:Transfection
chemical_list: D007328:Insulin; D004247:DNA; D011972:Receptor, Insulin