In-frame exon 2 deletion in insulin receptor RNA in a family with extreme insulin resistance in association with defective insulin binding: a case report.
In-frame exon 2 deletion in insulin receptor RNA in a family with extreme insulin resistance in association with defective insulin binding: a case report.
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与胰岛素结合缺陷相关的极端胰岛素抵抗家族中胰岛素受体 RNA 的框内外显子 2 缺失：病例报告。
DOI：
10.1530/eje.0.1350357
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发表时间：
1996
影响因子：
5.8
通讯作者：
J. Levy
中科院分区：
文献类型：
--
作者：
W. Moritz;M. Böni;W. Stevens;E. Froesch;J. Levy
胰岛素受体基因的表型和等位基因表达是在一个家庭与A型胰岛素抵抗患者。与对照组相比，转化淋巴细胞中的胰岛素受体结合率为100%。在父亲、母亲和先证者中分别为33%和13%。胰岛素受体结合减少与胰岛素受体mRNA表达改变共分离;母亲和女儿表达了8种胰岛素受体mRNA，包括一组4种正常大小的mRNA和一组4种较短的mRNA转录物。在先证者中，正常大小的mRNA转录物的水平相对于较短的转录物被抑制。逆转录聚合酶链反应（PCR）显示，较短的成绩单包含外显子2的框内缺失。对整个胰岛素受体编码区的测序显示，在核苷酸3205处存在父系遗传的A至T置换，将异亮氨酸996转化为苯丙氨酸，而苯丙氨酸不与降低的结合共分离。因此，我们假设有两个结果是必要的介绍A型胰岛素抵抗在这个病人：一个框内缺失的胰岛素受体外显子2编码的氨基酸胰岛素结合至关重要的：和抑制表达的父亲胰岛素受体等位基因。
The phenotype and allelic expression of the insulin receptor gene is presented in a family with a patient with type A insulin resistance. Compared to controls, insulin receptor binding in transformed lymphocytes was 100%. 33% and 13% in the father, mother and proband, respectively. Reduced insulin receptor binding co-segregated with altered insulin receptor mRNA expression; the mother and daughter expressed eight insulin receptor mRNA species, including a set of four normal sized and a set of four shorter mRNA transcripts. In the proband the levels of the normal sized mRNA transcripts were suppressed relative to the shorter transcripts. Reverse polymerase chain reaction (PCR) revealed that the shorter transcripts contained an in-frame deletion of exon 2. Sequencing of the entire insulin receptor coding region revealed a paternally inherited A to T substitution in nucleotide 3205, converting isoleucine 996 to phenylalanine, which does not co-segregate with reduced binding. Therefore, we hypothesize that two findings are necessary for the presentation of type A insulin resistance in this patient: an in-frame deletion of the insulin receptor exon 2 that codes for amino acids crucial for insulin binding: and an inhibition of expression of the paternal insulin receptor allele.