Moritz W, Böni-Schnetzler M, Stevens W, Froesch E R, Levy J R
Department of Internal Medicine, University Hospital, Zürich, Switzerland.
Eur J Endocrinol. 1996 Sep;135(3):357-63. doi: 10.1530/eje.0.1350357.
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.
在一个患有A型胰岛素抵抗患者的家族中，呈现了胰岛素受体基因的表型和等位基因表达情况。与对照组相比，转化淋巴细胞中胰岛素受体结合率在父亲、母亲和先证者中分别为100%、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种类，包括一组4种正常大小的和一组4种较短的mRNA转录本。在先证者中，正常大小的mRNA转录本水平相对于较短的转录本被抑制。逆转录聚合酶链反应（PCR）显示，较短的转录本包含外显子2的框内缺失。对整个胰岛素受体编码区进行测序发现，父亲遗传的第3205位核苷酸发生了A到T的替换，导致异亮氨酸996变为苯丙氨酸，该替换与结合减少不共分离。因此，我们推测该患者出现A型胰岛素抵抗需要两个条件：胰岛素受体外显子2的框内缺失，该外显子编码对胰岛素结合至关重要的氨基酸；以及父本胰岛素受体等位基因表达的抑制。
