Two mutant alleles of the insulin receptor gene in a patient with extreme insulin resistance

Takashi Kadowaki, Charles L Bevins, Alessandro Cama, Kaie Ojamaa, Bernice Marcus-Samuels, Hiroko Kadowaki, Laurie Beitz, Catherine Mckeon, Simeon I. Taylor

Research output: Contribution to journalArticle

234 Citations (Scopus)

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 α subunit of the receptor. The second allele has a nonsense mutation causing premature chain termination after amino acid 671 in the α 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.

Original languageEnglish (US)
Pages (from-to)787-790
Number of pages4
JournalScience
Volume240
Issue number4853
StatePublished - 1988
Externally publishedYes

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Insulin Receptor
Insulin Resistance
Nonsense Codon
Alleles
Donohue Syndrome
Insulin
Genes
Multiple Abnormalities
Receptor Protein-Tyrosine Kinases
Missense Mutation
Heterozygote
Fathers
Type 2 Diabetes Mellitus
Lysine
Glutamic Acid
Complementary DNA
Amino Acids
Mutation

ASJC Scopus subject areas

  • General

Cite this

Kadowaki, T., Bevins, C. L., Cama, A., Ojamaa, K., Marcus-Samuels, B., Kadowaki, H., ... Taylor, S. I. (1988). Two mutant alleles of the insulin receptor gene in a patient with extreme insulin resistance. Science, 240(4853), 787-790.

Two mutant alleles of the insulin receptor gene in a patient with extreme insulin resistance. / Kadowaki, Takashi; Bevins, Charles L; Cama, Alessandro; Ojamaa, Kaie; Marcus-Samuels, Bernice; Kadowaki, Hiroko; Beitz, Laurie; Mckeon, Catherine; Taylor, Simeon I.

In: Science, Vol. 240, No. 4853, 1988, p. 787-790.

Research output: Contribution to journalArticle

Kadowaki, T, Bevins, CL, Cama, A, Ojamaa, K, Marcus-Samuels, B, Kadowaki, H, Beitz, L, Mckeon, C & Taylor, SI 1988, 'Two mutant alleles of the insulin receptor gene in a patient with extreme insulin resistance', Science, vol. 240, no. 4853, pp. 787-790.
Kadowaki T, Bevins CL, Cama A, Ojamaa K, Marcus-Samuels B, Kadowaki H et al. Two mutant alleles of the insulin receptor gene in a patient with extreme insulin resistance. Science. 1988;240(4853):787-790.
Kadowaki, Takashi ; Bevins, Charles L ; Cama, Alessandro ; Ojamaa, Kaie ; Marcus-Samuels, Bernice ; Kadowaki, Hiroko ; Beitz, Laurie ; Mckeon, Catherine ; Taylor, Simeon I. / Two mutant alleles of the insulin receptor gene in a patient with extreme insulin resistance. In: Science. 1988 ; Vol. 240, No. 4853. pp. 787-790.
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