Bench meets bedside: A 10-year-old girl and amino acid residue glycine 75 of the facilitative glucose transporter GLUT1
Bench meets bedside: A 10-year-old girl and amino acid residue glycine 75 of the facilitative glucose transporter GLUT1
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DOI：
10.1021/bi051079t
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发表时间：
2005-09-27
期刊：
影响因子：
2.9
通讯作者：
Fischbarg, J
中科院分区：
文献类型：
--
作者：
Klepper, J;Salas-Burgos, A;Fischbarg, J
在2000年，通过诱变鉴定了促进性葡萄糖转运蛋白GLUT 1的氨基酸残基G75对于转运功能是必需的[Olsowski，A.，等人（2000）Biochemistry 39，2469-74]。在2002年，我们发现了一个杂合错义突变取代甘氨酸残基75色氨酸在一个10岁的女孩与顽固性癫痫发作和低血糖浓度的脑脊液中指示GLUT 1缺乏症。患者红细胞葡萄糖摄取为对照组的36%，GLUT 1特异性免疫反应性正常，表明功能性GLUT 1缺陷。G75 W突变体的计算机三维建模提供了跨膜片段2的较小回转半径作为该患者的潜在致病机制。该病例说明了GLUT 1突变在体外的特征，后来被疾病本身证实，并强调了基础科学和临床医学合作造福患者的潜力。
In 2000, amino acid residue G75 of the facilitative glucose transporter GLUT1 was identified by mutagenesis as being essential for transport function [Olsowski, A., et al. (2000) Biochemistry 39, 2469-74]. In 2002, we identified a heterozygous missense mutation substituting glycine at residue 75 for tryptophan in a 10-year-old girl with intractable seizures and low glucose concentrations in the cerebrospinal fluid indicative of GLUT1 deficiency. Glucose uptake into erythrocytes of the patient was 36% of controls, and GLUT1-specific immunoreactivity was normal, indicating a functional GLUT1 defect. In silico three-dimensional modeling of the G75W mutant provided a smaller gyration radius for transmembrane segment 2 as the potential pathogenic mechanism in this patient. This case illustrates a GLUT1 mutation characterized in vitro and later confirmed by disease itself and highlights the potential of basic science and clinical medicine to collaborate for the benefit of patients.