Publication Date:
1988-05-06
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kadowaki, T -- Bevins, C L -- Cama, A -- Ojamaa, K -- Marcus-Samuels, B -- Kadowaki, H -- Beitz, L -- McKeon, C -- Taylor, S I -- New York, N.Y. -- Science. 1988 May 6;240(4853):787-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biochemistry and Molecular Pathophysiology Section, National Institute of Diabetes, Digestive, and Kidney Disease, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2834824" target="_blank"〉PubMed〈/a〉
Keywords:
Alleles
;
Base Sequence
;
Cell Line
;
Cell Membrane/metabolism
;
Cell Transformation, Viral
;
DNA/genetics
;
Diabetes Mellitus, Type 2/*genetics
;
Endocrine System Diseases/genetics
;
Female
;
Gene Amplification
;
Growth Disorders/genetics
;
Herpesvirus 4, Human
;
Heterozygote
;
Humans
;
Hydrogen-Ion Concentration
;
Insulin/blood
;
Insulin Resistance/*genetics
;
Lymphocytes/metabolism
;
Monocytes/metabolism
;
Mutation
;
Receptor, Insulin/*genetics
;
Syndrome
;
Transfection
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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