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

238 Scopus citations

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