title: Bench meets bedside: a 10-year-old girl and amino acid residue glycine 75 of the facilitative glucose transporter GLUT1.
abstract: 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.
authors.affiliation: Department of Pediatrics and Pediatric Neurology, University of Essen, Hufelandstrasse 55, D-45122 Essen, Germany. joerg.klepper@uni-essen.de
authors.forename: Jörg
authors.initials: J
authors.lastname: Klepper
authors.forename: Alexis
authors.initials: A
authors.lastname: Salas-Burgos
authors.forename: Elena
authors.initials: E
authors.lastname: Gertsen
authors.forename: Jorge
authors.initials: J
authors.lastname: Fischbarg
mesh_terms: D019325:3-O-Methylglucose / Q000378:metabolism; D000595:Amino Acid Sequence; D002648:Child; D004827:Epilepsy / Q000235:genetics*; D005260:Female; D005998:Glycine / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D013577:Syndrome
chemical_list: D019325:3-O-Methylglucose; D005998:Glycine