Abstract.
Galactosemia is a metabolic disorder caused by a defect in the galactose-1-phosphate uridyltransferase (GALT) enzyme. In previous studies, we have shown that the presence of a deletion in the 5′ upstream (promoter) region of the GALT gene is associated with the Duarte (D2) allele. In the present study, by using a promoter fusion assay we provide direct evidence that a GTCA deletion located in position –119/–116 of the GALT gene (considered in relation to the translational start site) decreases transcription of a reporter gene to about 55% compared with a normal "healthy" promoter transfected into human hepatocyte HepG2 cells. This result coincides well with previously published biochemical data showing 50% GALT-gene activity in Duarte (D2) galactosemia patients. By transfecting the same promoters (normal and deleted) into mouse NIH/3T3 cells, we show that the GTCA motif in the promoter region of the GALT gene was conserved throughout evolution. We conclude that the –119/–116delGTCA promoter mutation is a crucial factor in reduction of Duarte allele enzyme activity.
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Trbušek, M., Francová, H. & Kozák, L. Galactosemia: deletion in the 5′ upstream region of the GALT gene reduces promoter efficiency. Hum Genet 109, 117–120 (2001). https://doi.org/10.1007/s004390100540
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DOI: https://doi.org/10.1007/s004390100540