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Functional consequences of the autosomal dominant G272A mutation in the human GLUT1 gene
Author(s) -
Klepper Jörg,
Monden Ingrid,
Guertsen Elena,
Voit Thomas,
Willemsen Michèl,
Keller Konrad
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02463-2
Subject(s) - glut1 , missense mutation , mutant , xenopus , mutation , alanine , glucose transporter , genetics , gene , biology , microbiology and biotechnology , mutagenesis , glycine , glucose transporter type 1 , biochemistry , chemistry , amino acid , endocrinology , insulin
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.