2 MUTANT ALLELES OF THE INSULIN-RECEPTOR GENE IN A PATIENT WITH EXTREME INSULIN RESISTANCE
2 MUTANT ALLELES OF THE INSULIN-RECEPTOR GENE IN A PATIENT WITH EXTREME INSULIN RESISTANCE
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DOI：
10.1126/science.2834824
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发表时间：
1988-05-06
期刊：
影响因子：
56.9
通讯作者：
TAYLOR, SI
中科院分区：
文献类型：
--
作者：
KADOWAKI, T;BEVINS, CL;TAYLOR, SI
从一个胰岛素抵抗的小妖精患者身上克隆出胰岛素受体互补DNA，该患者的受体在胰岛素结合中表现出多种异常。该患者为复合杂合子，遗传了胰岛素受体基因的两个不同突变等位基因。其中一个等位基因包含一个错义突变，该突变编码了α基因中460号位置的谷氨酸取代赖氨酸。受体的亚基。第二个等位基因有一个无义突变，导致在。α的671个氨基酸后过早终止链。亚基，从而删除受体的跨膜和酪氨酸激酶结构域。有趣的是，这个无义突变的父亲是杂合的，并表现出中等程度的胰岛素抵抗。这就提出了胰岛素受体基因突变可能是一些非胰岛素依赖型糖尿病患者胰岛素抵抗的原因。
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.