Kadowaki T, Bevins C L, Cama A, Ojamaa K, Marcus-Samuels B, Kadowaki H, Beitz L, McKeon C, Taylor S I
Biochemistry and Molecular Pathophysiology Section, National Institute of Diabetes, Digestive, and Kidney Disease, Bethesda, MD 20892.
Science. 1988 May 6;240(4853):787-90. doi: 10.1126/science.2834824.
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.
已从一名患有类矮小症的胰岛素抵抗患者中克隆出胰岛素受体互补DNA，该患者的受体在胰岛素结合方面表现出多种异常。该患者是复合杂合子，继承了胰岛素受体基因的两个不同突变等位基因。一个等位基因包含一个错义突变，编码受体α亚基第460位赖氨酸被谷氨酸替代。第二个等位基因有一个无义突变，导致α亚基第671位氨基酸后链提前终止，从而缺失受体的跨膜和酪氨酸激酶结构域。有趣的是，父亲是这种无义突变的杂合子，表现出中度胰岛素抵抗。这增加了胰岛素受体基因突变可能是某些非胰岛素依赖型糖尿病患者胰岛素抵抗原因的可能性。
