Kasuga M, Kishimoto M, Hashiramoto M, Yonezawa K, Kazumi T, Hagino H, Shii K
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Nihon Geka Gakkai Zasshi. 1992 Sep;93(9):968-71.
A novel mutation Arg1131-->Gln in the catalytic loop of insulin receptor (IR) associated with insulin resistant diabetes was detected. A 56-year-old male with hyperinsulinemia (fasting IRI 92 microU/ml) showed moderate impairment in glucose tolerance (HbAlc 7.0%, fructosamine 258 mumol/l, fasting glucose 119 mg/dl, maximum value of blood glucose during 75 g OGTT 220 mg/dl). While insulin binding to erythrocytes IR was normal, the insulin-induced autophosphorylation of the patient's erythrocytes IR in vivo showed marked decrease, suggesting this patient had some defect in the kinase domain (exon 17-21) of IR. PCR-SSCP analysis of kinase domain with a genomic DNA obtained from the patient's leucocytes indicated the presence of some mutations in exon 19. Sequencing analysis in M13 revealed a heterozygous mutation at a position 1131 (CGG-->CAG) substituting Gln for Arg. Four people of patient's family analyzed are revealed to have an identical missense mutation at the same position with the patient.
在胰岛素受体（IR）催化环中检测到一种与胰岛素抵抗性糖尿病相关的新型突变Arg1131→Gln。一名56岁男性，患有高胰岛素血症（空腹IRI 92微单位/毫升），糖耐量有中度受损（糖化血红蛋白7.0%，果糖胺258微摩尔/升，空腹血糖119毫克/分升，75克口服葡萄糖耐量试验期间血糖最大值220毫克/分升）。虽然胰岛素与红细胞IR的结合正常，但患者红细胞IR在体内的胰岛素诱导自磷酸化显著降低，提示该患者IR的激酶结构域（外显子17 - 21）存在某种缺陷。用从患者白细胞获得的基因组DNA对激酶结构域进行PCR - SSCP分析表明外显子19存在一些突变。M13测序分析显示在1131位（CGG→CAG）有一个杂合突变，使精氨酸被谷氨酰胺取代。对患者家族中的4人进行分析，发现他们在同一位置与患者有相同的错义突变。
