title: Genetic basis of galactosemia.
abstract: Classic galactosemia is an inborn error of galactose metabolism and results from deficiency of the ubiquitously expressed enzyme galactose-1-phosphate uridyltransferase (GALT). Nine missense mutations, three splicing mutations, three GALT protein polymorphisms, and one silent nucleotide substitution have been identified to date. Most of the disease-causing mutations are rare among patients. The most common mutation, Q188R, has a frequency of only one-fourth in the patient population examined. Three classes of disease-causing mutations have been reported: CRM+ missense mutations (the most common class), CRM- missense mutations, and splicing mutations. Thus, galactosemia is heterogeneous at the molecular level, which is noteworthy in light of the well-documented clinical variability observed in this disorder. It has also been shown that eight of nine galactosemia missense mutations occur in evolutionarily well-conserved domains, suggesting that they affect functionally and/or structurally important residues. In contrast, all protein polymorphisms alter variable amino acids which presumably are not important for the enzyme's function.
authors.affiliation: Howard Hughes Medical Institute, Baylor College of Medicine, Texas Medical Center, Houston 77030-3498.
authors.forename: J K
authors.initials: JK
authors.lastname: Reichardt
mesh_terms: D000595:Amino Acid Sequence; D005260:Female; D005693:Galactosemias / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011296:Prenatal Diagnosis; D044469:Racial Groups / Q000235:genetics; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000172:deficiency / Q000235:genetics
chemical_list: D005694:UTP-Hexose-1-Phosphate Uridylyltransferase