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rdf:type |
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lifeskim:mentions |
umls-concept:C0016952,
umls-concept:C0016953,
umls-concept:C0017337,
umls-concept:C0026882,
umls-concept:C0086418,
umls-concept:C0679058,
umls-concept:C1414962,
umls-concept:C1547699,
umls-concept:C1853126,
umls-concept:C1882417,
umls-concept:C2700640
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pubmed:issue |
7
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pubmed:dateCreated |
1991-5-6
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pubmed:abstractText |
We describe the molecular characterization of two mutations responsible for galactosemia, an inherited disorder of galatose metabolism that causes jaundice, cataracts, and mental retardation in humans. The coding region of galactose-1-phosphate uridylyltransferase (GALT; UDPglucose:alpha-D-galactose-1-phosphate uridylyltransferase, EC 2.7.7.12) was amplified by the polymerase chain reaction from total cDNA of a classic galactosemic individual and was characterized by direct sequencing of the products. Two missense mutations were identified: (i) replacement of valine-44 by methionine and (ii) replacement of methionine-142 by lysine. These mutations led to a drastic reduction in GALT activity when individual mutant cDNAs were overexpressed in a mammalian cell system, although full-length protein is synthesized in this assay. The two galactosemia mutations account for 3 of the 15 galactosemia alleles analyzed. These results suggest that galactosemia is caused by a variety of mutations, which might be responsible for the observed clinical heterogeneity of this disorder. We also present the molecular characterization of two GALT polymorphisms: (i) replacement of leucine-62 by methionine and (ii) replacement of asparagine-314 by aspartate. It appears that galactosemia mutations tend to occur in regions that are highly conserved throughout evolution while the polymorphisms change variable residues.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574-2233247,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574-2475911,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574-2565120,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574-2570460,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574-2696185,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574-2740244,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574-2840550,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574-2845364,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574-2907192,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574-3022232,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574-3071259,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574-3076300,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574-3149806,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574-3338800,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574-3380691,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574-3419917,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574-518835,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574-59400,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574-6084979,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574-6479120,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011574-660351
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
88
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2633-7
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:2011574-Amino Acid Sequence,
pubmed-meshheading:2011574-Animals,
pubmed-meshheading:2011574-Base Sequence,
pubmed-meshheading:2011574-Cell Line,
pubmed-meshheading:2011574-DNA,
pubmed-meshheading:2011574-Galactosemias,
pubmed-meshheading:2011574-Genes,
pubmed-meshheading:2011574-Genetic Variation,
pubmed-meshheading:2011574-Humans,
pubmed-meshheading:2011574-Molecular Sequence Data,
pubmed-meshheading:2011574-Mutagenesis, Site-Directed,
pubmed-meshheading:2011574-Mutation,
pubmed-meshheading:2011574-Oligonucleotide Probes,
pubmed-meshheading:2011574-Polymerase Chain Reaction,
pubmed-meshheading:2011574-Polymorphism, Genetic,
pubmed-meshheading:2011574-Transfection,
pubmed-meshheading:2011574-UTP-Hexose-1-Phosphate Uridylyltransferase
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pubmed:year |
1991
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pubmed:articleTitle |
Molecular basis of galactosemia: mutations and polymorphisms in the gene encoding human galactose-1-phosphate uridylyltransferase.
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pubmed:affiliation |
Howard Hughes Medical Institute, Department of Cell Biology, Houston, TX.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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