Functional consequences of the autosomal dominant G272A mutation in the human GLUT1 gene

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.