HUMAN UDP-GALACTOSE 4'-EPIMERASE (GALE) GENE AND IDENTIFICATION OF 5 MISSENSE MUTATIONS IN PATIENTS WITH EPIMERASE-DEFICIENCY GALACTOSEMIA

The galactosemias are a series of three inborn errors of metabolism ca used by deficiency of any one of the three human galactose-metabolic e nzymes: galactokinase (GALK), galactose-1-phosphate uridyl transferase (GALT), and UDP-galactose 4' epimerase (GALE). We report here the cha racterization of the entire coding sequence of the GALE gene and scree ning for mutations in epimerase-deficient individuals. The human GALE gene is about 4 kb in size and is divided into 11 exons on chromosome band 1p36. We have identified five mutations in the GALE gene of epime rase-deficient galactosemia patients. The patients were either homozyg otes or compound heterozygotes for mutations. These results confirm th at epimerase-deficiency galactosemia is the result of missense mutatio ns in the GALE gene and indicate that the disease is characterized by extensive allelic heterogeneity. (C) 1998 Academic Press.