Linked Life Data

18346471

Source:http://linkedlifedata.com/resource/pubmed/id/18346471

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-5-21
pubmed:abstractText
Hyperphenylalaninemia is a group of autosomal recessive disorders caused by a wide range of phenylalanine hydroxylase (PAH) gene variants. To study the effects of mutations on PAH activity, we have reproduced five mutations (p.N223Y, p.R297L, p.F382L, p.K398N and p.Q419R) that we recently identified in a population of Southern Italy. Transient expression of mutant full-length cDNAs in human HEK293 cells yielded PAH variants whose l-phenylalanine hydroxylase activity was between 40% and 70% that of the wild-type enzyme. Moreover, Western blot analysis revealed a 50-kD monomer in all mutants thereby indicating normal synthesis of the mutant proteins. Because of the clinical mild nature of the phenotypes we performed an in vivo BH4 loading test. This was positive in all tested patients, which indicates that they are likely to respond to the coenzyme in vivo. We also analysed the environment of each mutation site in the available crystal structures of PAH by using molecular graphics tools. The structural alteration produced by each mutation was elucidated and correlated to the mutated properties of the mutant enzymes. All the data obtained demonstrate the disease-causing nature of the five novel variants.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:volume
1782
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
378-84
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Five human phenylalanine hydroxylase proteins identified in mild hyperphenylalaninemia patients are disease-causing variants.
pubmed:affiliation
CEINGE - Biotecnologie Avanzate Scarl, Via Comunale Margherita, 482, 80145, Naples, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't