Shimada F, Suzuki Y, Taira M, Hashimoto N, Nozaki O, Makino H, Yoshida S
Second Department of Internal Medicine, Chiba University School of Medicine, Japan.
Diabetologia. 1992 Jul;35(7):639-44. doi: 10.1007/BF00400255.
In a previous report on a 16-year-old Japanese girl with type A insulin resistance, we found that one allele of the insulin receptor gene was inherited from her mother and contained a 1.2 kilobase pair deletion which removed the 14th exon in the beta subunit. We extended investigation of the proband and found the deletion between two Alu sequences. To determine the effect of the deletion on the level of transcription and the splicing pattern of messenger ribonucleic acid (mRNA), we synthesized the complimentary DNA and used the polymerase chain reaction to amplify the region which included the deleted area. The deletion shifted the reading frame, resulting in a termination codon after amino acid 867 (Glu), thereby producing a truncated insulin receptor without a transmembrane region and cytoplasmic domain. We also sequenced each of 22 exons of the insulin receptor gene but found no mutation in exons of the insulin receptor gene, except for deletion of exon 14 of the maternal allele. Thus, the proband is a heterozygote for a single mutant allele. Abnormal mRNA transcribed from the mutant allele resulted in a decrease in insulin binding.
在之前一份关于一名患有A型胰岛素抵抗的16岁日本女孩的报告中，我们发现胰岛素受体基因的一个等位基因是从她母亲那里遗传而来的，并且包含一个1.2千碱基对的缺失，该缺失去除了β亚基中的第14外显子。我们对先证者进行了进一步研究，发现该缺失位于两个Alu序列之间。为了确定该缺失对信使核糖核酸（mRNA）转录水平和剪接模式的影响，我们合成了互补DNA，并使用聚合酶链反应扩增包含缺失区域的片段。该缺失导致阅读框移位，在氨基酸867（Glu）之后产生一个终止密码子，从而产生一个没有跨膜区域和胞质结构域的截短胰岛素受体。我们还对胰岛素受体基因的22个外显子逐一进行了测序，但发现除了母本等位基因的第14外显子缺失外，胰岛素受体基因的外显子没有其他突变。因此，先证者是单一突变等位基因的杂合子。从突变等位基因转录而来的异常mRNA导致胰岛素结合减少。
