Linked Life Data

10479481

Source:http://linkedlifedata.com/resource/pubmed/id/10479481

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-10-19
pubmed:abstractText
Phenylketonuria and mild hyperphenylalaninemias are allelic disorders caused by mutations in the phenylalanine hydroxylase (PAH) gene. Following identification of the disease-causing mutation in 11 PAH-deficient patients, we tested the activity of the mutant gene products in an eukaryotic expression system. Two mutations markedly reduced PAH activity (A259V and L333F), one mutation mildly altered the enzyme activity (E390G), while the majority of mutant genotypes reduced the in vitro expression of PAH activity to 15-30% of controls. Comparing the predicted residual activity derived from expression studies to the clinical phenotypes of our PAH-deficient patients, we found that homozygosity for the L333F and E390G mutations resulted in severe and mild PAH deficiencies, respectively, both in vivo and in vitro, while compound heterozygosity (L333F/E390G) resulted in an intermediate dietary tolerance. Similarly, in vitro expression studies largely predicted dietary tolerance in compound heterozygotes for the A259V/IVS12nt1 (typical PKU), A259V/A403V, G218V/I65T, and G218V/R158Q mutations (mild variants). Taken together, these results support the view that expression studies are useful in predicting residual enzyme activity and that the mutant genotype at the PAH locus is the major determinant of metabolic phenotype in hyperphenylalaninemias.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1096-7192
pubmed:author
pubmed:copyrightInfo
Copyright 1999 Academic Press.
pubmed:issnType
Print
pubmed:volume
68
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
43-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
The mutant genotype is the main determinant of the metabolic phenotype in phenylalanine hydroxylase deficiency.
pubmed:affiliation
Department of Genetics and Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, Hôpital des Enfants-Malades, 149 rue de Sèvres, Paris Cedex 15, 75743, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't