Genomics. 1992 Mar;12(3):596-600.

Characterization of two missense mutations in human galactose-1-phosphate uridyltransferase: different molecular mechanisms for galactosemia.

Reichardt JK, Belmont JW, Levy HL, Woo SL.

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Howard Hughes Medical Institute, Department of Cell Biology, Baylor College of Medicine, Texas Medical Center, Houston 77030-3498.

Abstract

We report the molecular characterization of two novel galactosemia mutations that exhibit different molecular phenotypes. Both are of the missense type with low or no residual enzyme activity. The R148W mutation results in an unstable protein, although messenger RNA is still produced. In contrast, the L195P mutation produces stable but inactive immunoreactive protein. The R148W mutation alters an amino acid that is not evolutionarily conserved, while the L195P mutation affects a well-conserved residue nine amino acids down-stream from the putative active site nucleophile. These mutations provide evidence that different mechanisms can result in galactosemia: destabilizing mutations in any given area of the protein and missense mutations in conserved domains of the enzyme resulting in low or no activity. These two mutant alleles represent the fifth and sixth galactosemia mutations and confirm the hypothesis that galactosemia results from a multiplicity of mutations at the molecular level.

PMID:: 1373122; [PubMed - indexed for MEDLINE]

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Molecular characterization of two galactosemia mutations and one polymorphism: implications for structure-function analysis of human galactose-1-phosphate uridyltransferase. [Biochemistry. 1992]
Molecular characterization of two galactosemia mutations and one polymorphism: implications for structure-function analysis of human galactose-1-phosphate uridyltransferase.
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Cited by 4 PubMed Central articles

A yeast expression system for human galactose-1-phosphate uridylyltransferase. [Proc Natl Acad Sci U S A. 1993]
A yeast expression system for human galactose-1-phosphate uridylyltransferase.
Fridovich-Keil JL, Jinks-Robertson S. Proc Natl Acad Sci U S A. 1993 Jan 15; 90(2):398-402.
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Identification and functional analysis of three distinct mutations in the human galactose-1-phosphate uridyltransferase gene associated with galactosemia in a single family.
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Galactosemia: a strategy to identify new biochemical phenotypes and molecular genotypes. [Am J Hum Genet. 1995]
Galactosemia: a strategy to identify new biochemical phenotypes and molecular genotypes.
Elsas LJ, Langley S, Steele E, Evinger J, Fridovich-Keil JL, Brown A, Singh R, Fernhoff P, Hjelm LN, Dembure PP. Am J Hum Genet. 1995 Mar; 56(3):630-9.

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