| A yeast model reveals biochemical severity associated with each of three variant alleles of galactose-1P uridylyltransferase segregating in a single family. | |
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MedLine Citation:
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PMID: 18210213 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Classic galactosaemia is a potentially lethal inborn error of metabolism that results from profound impairment of galactose-1P uridylyltransferase (GALT). Like many autosomal recessive disorders, classic galactosaemia demonstrates marked allelic heterogeneity; many if not most patients are compound heterozygotes. Owing in part to the fact that most GALT mutations are never observed in patients in the homozygous state, in part to concerns of possible allelic interaction, and in part to the broad range of GALT activity levels associated with the affected, carrier, and control states, definition of the specific functional consequence of individual variant GALT alleles from studies of clinical samples alone can be a challenging task. To overcome this problem we previously developed and applied a null-background yeast system to enable functional analyses of human GALT alleles expressed individually or in defined pairs. We report here the application of this system to characterize three distinct variant alleles of GALT identified within a single family. Of these alleles, one carried a missense mutation (K285N) that has previously been reported and characterized, one carried a nonsense mutation (R204X) that has previously been reported but not characterized, and the third carried a missense substitution (T268N) that was novel. Our studies reported here reconfirm the profound nature of the K285N mutation, demonstrate that the R204X mutation severely compromises both expression and function of human GALT, and finally implicate T268N as one of a very small number of naturally occurring rare but neutral missense polymorphisms in human GALT. |
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Authors:
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J S Chhay; K K Openo; J S Eaton; M Gentile; J L Fridovich-Keil |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-01-22 |
Journal Detail:
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Title: Journal of inherited metabolic disease Volume: 31 ISSN: 1573-2665 ISO Abbreviation: J. Inherit. Metab. Dis. Publication Date: 2008 Feb |
Date Detail:
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Created Date: 2008-03-10 Completed Date: 2008-06-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7910918 Medline TA: J Inherit Metab Dis Country: Netherlands |
Other Details:
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Languages: eng Pagination: 97-107 Citation Subset: IM |
Affiliation:
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Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alleles* Case-Control Studies Cells, Cultured Chromosome Segregation / physiology Family Galactose / pharmacology Galactosemias / classification, genetics* Gene Expression Regulation, Fungal / drug effects Genetic Heterogeneity Humans Lymphocytes / enzymology, metabolism Models, Biological* Mutation, Missense / physiology Pedigree Severity of Illness Index Transfection UDPglucose-Hexose-1-Phosphate Uridylyltransferase / genetics* Yeasts / genetics* |
| Chemical | |
Reg. No./Substance:
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26566-61-0/Galactose; EC 2.7.7.12/UDPglucose-Hexose-1-Phosphate Uridylyltransferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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