On the molecular nature of the Duarte variant of galactose-1-phosphate uridyl transferase (GALT)
- 84 Downloads
- 16 Citations
Abstract
Galactosemia is an inborn error of galactose metabolism secondary to deficiency of galactose-1-phosphate uridyl transferase (GALT). GALT is a polymorphic enzyme and Duarte (D) is the most common enzyme variant. This variant is characterized by faster electrophoretic mobility and reduced activity. Duarte/galactosemia compound heterozygotes (D/G) are commonly identified in galactosemia newborn screening programs. However, these patients do not generally require treatment. By using a “candidate mutation” approach to define the molecular basis of the Duarte variant of GALT, a close association between the previously reported N314D polymorphism and the Duarte variant of GALT was found. We suggest that N314D encodes the D variant of GALT and that molecular testing for N314D might be useful to confirm a biochemical diagnosis of Duarte variant of GALT.
Keywords
Galactose Screening Program Electrophoretic Mobility Newborn Screening Inborn ErrorPreview
Unable to display preview. Download preview PDF.
References
- Banroques J, Gregori C, Schapira F (1981) Purification and characterization of human erythrocyte uridylyl transferase. Biochim Biophys Acta 657:374–382Google Scholar
- Beutler E, Baluda MC (1966) Biochemical properties of human red cell galactose-1-phosphate uridyl transferase (UDP glucose: a D-galactose-1-phosphate uridyltransferase E. C. 2.7.7.12) from normal and mutant subjects. J Lab Clin Med 67:947–954Google Scholar
- Flach JE, Reichardt JKV, Elsas LJ (1990) Sequence of a cDNA encoding human galactose-1-phosphate uridyl transferase. Mol Biol Med 7:365–369Google Scholar
- Kelley RI, Harris H, Mellman WJ (1983) Characterization of normal and abnormal variants of galactose-1-phosphate uridylyltransferase (EC 2.7.7.12) by isoelectric focusing. Hum Genet 63:274–279Google Scholar
- Lee JES, Ng WG (1982) Semi-micro techniques for genotyping of galactokinase and galactose-1-phosphate uridyltransferase. Clin Chim Acta 124:351–356Google Scholar
- Leslie ND, Immerman EB, Flach JE, Florez M, Fridovich-Keil JL, Elsas LJ (1992) The human galactose-1-phosphate uridyl transferase gene. Genomics 14:474–480Google Scholar
- Mathai CK, Beutler E (1966) Electrophoretic variation of galactose-1-phosphate uridyltransferase. Science 154:1179–1180Google Scholar
- Ng WG, Bergren WR, Fields M, Donnell GN (1969) An improved electrophoretic procedure for galactose-1-phosphate uridyl transferase: demonstration of multiple activity bands with the Duarte variant. Biochem Biophys Res Commun 37:354–362Google Scholar
- Ng WG, Bergren WR, Donnell GN (1972) A new variant of galactose-1-phosphate uridyltransferase in man: the Los Angeles variant. Ann Hum Genet 37:1–8Google Scholar
- Reichardt JKV (1992) Genetic basis of galactosemia. Hum Mutat 1:190–196Google Scholar
- Reichardt JKV, Berg P (1988) Cloning and characterization of a cDNA encoding human galactose-1-phosphate uridyl transferase. Mol Biol Med 5:107–122Google Scholar
- Reichardt JKV, Woo SLC (1991) Molecular basis of galactosemia: mutations and polymorphisms in the gene encoding human galactose-1-phosphate uridylyltransferase. Proc Natl Acad Sci USA 88:2633–2637Google Scholar
- Segal S (1989) Disorders of galactose metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill, New York, pp 453–480Google Scholar
- Shin YS, Niedermeier HP, Endres W, Schaub J, Weidinger S (1987) Agarose gel isoelectrofocusing of UDP-galactose pyrophosphorylase and galactose-1-phosphate uridyltransferase: developmental aspect of UDP-galactose pyrophosphorylase. Clin Chim Acta 166:27–35Google Scholar
- Williams VP, Helmer GR, Fried C (1982) Human galactose-1-phosphate uridylyltransferase: purification and comparison of the red blood cell and placental enzymes. Arch Biochem Biophys 216:503–511Google Scholar