title: Functional consequences of the autosomal dominant G272A mutation in the human GLUT1 gene.
abstract: The first autosomal dominant missense mutation (G272A) reported within the human GLUT1 gene and shared by three affected family members was investigated in respect to functional consequences. Substitution of glycine-91 by site-directed mutagenesis with either aspartate or alanine resulted in a significant decrease in transport activity of GLUT1 expressed in Xenopus oocytes. Expression of mutant transporters was confirmed by immunoblot, 2-deoxy-glucose uptake and confocal laser microscopy. The data agree with 3-O-methyl-glucose uptake into patient erythrocytes and indicate that the loss of glycine rather than a hydrophilic side chain (Gly91Asp) defines the functional consequences of this mutation.
authors.affiliation: Department of Pediatrics and Pediatric Neurology, University of Essen, Germany. joerg.klepper@uni-essen.de
authors.forename: J
authors.initials: J
authors.lastname: Klepper
authors.forename: I
authors.initials: I
authors.lastname: Monden
authors.forename: E
authors.initials: E
authors.lastname: Guertsen
authors.forename: T
authors.initials: T
authors.lastname: Voit
authors.forename: M
authors.initials: M
authors.lastname: Willemsen
authors.forename: K
authors.initials: K
authors.lastname: Keller
mesh_terms: D000409:Alanine / Q000235:genetics; D019943:Amino Acid Substitution; D000818:Animals; D002384:Catalysis; D004252:DNA Mutational Analysis; D051272:Glucose Transporter Type 1; D005998:Glycine / Q000235:genetics; D006801:Humans; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000502:physiology; D009865:Oocytes / Q000378:metabolism; D014162:Transfection; D014982:Xenopus laevis
chemical_list: D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human; D000409:Alanine; D005998:Glycine