The human galactose-1-phosphate uridyltransferase gene.
Classical galactosemia is an inborn error of metabolism caused by a deficiency of galactose-1-phosphate uridyltransferase (GALT). Standard treatment with dietary galactose restriction will reverse the potentially lethal symptoms of the disease that are manifest in the newborn period. However, the long-term prognosis for these patients is variable. As a first step toward investigating the molecular basis for phenotypic variation in galactosemia, we have cloned and sequenced the entire gene for human galactose-1-phosphate uridyltransferase. This gene is organized into 11 exons spanning 4 kb. In exons 6, 9, and a portion of 10, there is a high degree of amino acid sequence conservation among Escherichia coli, yeast, mouse, and human. We have identified a number of nucleotide changes in the GALT genes of galactosemic patients that alter conserved amino acids. The most common of these is an A to G transition at nucleotide position 1470, converting a glutamine to an arginine at amino acid codon position 188 (Q188R).(ABSTRACT TRUNCATED AT 250 WORDS)
Leslie
N D
ND
Basic Science Research, Children's Hospital Research Foundation, Cincinnati, Ohio 45229.
Immerman
E B
EB
Flach
J E
JE
Florez
M
M
Fridovich-Keil
J L
JL
Elsas
L J
LJ
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D004247:DNA; D005693:Galactosemias / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000235:genetics*
D004247:DNA; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase