Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1992-12-22
|
| pubmed:abstractText |
Nonphenylketonuria hyperphenylalaninemia (non-PKU HPA) is defined as phenylalanine hydroxylase (PAH) deficiency with blood phenylalanine levels below 600 mumol/liter (i.e., within the therapeutic range) on a normal dietary intake. Haplotype analysis at the PAH locus was performed in 17 Danish families with non-PKU HPA, revealing compound heterozygosity in all individuals. By allele-specific oligonucleotide (ASO) probing for common PKU mutations we found 12 of 17 non-PKU HPA children with a PKU allele on one chromosome. To identify molecular lesions in the second allele, individual exons were amplified by polymerase chain reaction and screened for mutations by single-strand conformation polymorphism. Two new missense mutations were identified. Three children had inherited a G-to-A transition at codon 415 in exon 12 of the PAH gene, resulting in the substitution of asparagine for aspartate, whereas one child possessed an A-to-G transition at codon 306 in exon 9, causing the replacement of an isoleucine by a valine in the enzyme. It is further demonstrated that the identified mutations have less impact on the heterozygote's ability to hydroxylate phenylalanine to tyrosine compared to the parents carrying a PKU mutation. The combined effect on PAH activity explains the non-PKU HPA phenotype of the child. The present observations that PKU mutations in combination with other mutations result in the non-PKU HPA phenotype and that particular mutation-restriction fragment length polymorphism haplotype combinations are associated with this phenotype offer the possibility of distinguishing PKU patients from non-PKU individuals by means of molecular analysis of the hyperphenylalaninemic neonate and, consequently, of determining whether a newborn child requires dietary treatment.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
0888-7543
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
14
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1-5
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:1358789-Base Sequence,
pubmed-meshheading:1358789-Exons,
pubmed-meshheading:1358789-Female,
pubmed-meshheading:1358789-Haplotypes,
pubmed-meshheading:1358789-Humans,
pubmed-meshheading:1358789-Infant, Newborn,
pubmed-meshheading:1358789-Male,
pubmed-meshheading:1358789-Metabolism, Inborn Errors,
pubmed-meshheading:1358789-Molecular Sequence Data,
pubmed-meshheading:1358789-Oligonucleotide Probes,
pubmed-meshheading:1358789-Pedigree,
pubmed-meshheading:1358789-Phenylalanine,
pubmed-meshheading:1358789-Phenylalanine Hydroxylase,
pubmed-meshheading:1358789-Phenylketonurias,
pubmed-meshheading:1358789-Point Mutation,
pubmed-meshheading:1358789-Polymerase Chain Reaction,
pubmed-meshheading:1358789-Polymorphism, Restriction Fragment Length,
pubmed-meshheading:1358789-Tyrosine
|
| pubmed:year |
1992
|
| pubmed:articleTitle |
Molecular basis for nonphenylketonuria hyperphenylalaninemia.
|
| pubmed:affiliation |
John F. Kennedy Institute, Glostrup, Denmark.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|