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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
|
| pubmed:dateCreated |
1997-1-16
|
| pubmed:abstractText |
Tyrosine hydroxylase (TH) catalyzes the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-DOPA), the rate-limiting step in the biosynthesis of dopamine. This report describes a missense point mutation in the human TH (hTH) gene in a girl presenting parkinsonian symptoms in early infancy and a very low level of the dopamine metabolite homovanillic acid in the CSF. DNA sequencing revealed a T614-to-C transition in exon 5 (L205P). Both parents and the patient's brother are heterozygous for the mutation. Site-directed mutagenesis and expression in different systems revealed that the recombinant mutant enzyme had a low homospecific activity, i.e. approximately 1.5% of wt-hTH in E. coli and approximately 16% in a cell-free in vitro transcription-translation system. When transiently expressed in human embryonic kidney (A293) cells a very low specific activity (approximately 0.3% of wt-hTH) and immunoreactive hTH (< 2%) was obtained. The expression studies are compatible with the severe clinical phenotype of the L205P homozygous patient carrying this recessively inherited mutation. Treatment with L-DOPA resulted in normalisation of the CSF homovanillic acid concentration and a sustained improvement in parkinsonian symptoms.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0964-6906
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
5
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1023-8
|
| pubmed:dateRevised |
2009-9-29
|
| pubmed:meshHeading |
pubmed-meshheading:8817341-Cell Line,
pubmed-meshheading:8817341-DNA Mutational Analysis,
pubmed-meshheading:8817341-Escherichia coli,
pubmed-meshheading:8817341-Exons,
pubmed-meshheading:8817341-Female,
pubmed-meshheading:8817341-Gene Expression,
pubmed-meshheading:8817341-Genes,
pubmed-meshheading:8817341-Humans,
pubmed-meshheading:8817341-Infant,
pubmed-meshheading:8817341-Kidney,
pubmed-meshheading:8817341-Levodopa,
pubmed-meshheading:8817341-Molecular Weight,
pubmed-meshheading:8817341-Parkinson Disease,
pubmed-meshheading:8817341-Point Mutation,
pubmed-meshheading:8817341-RNA, Messenger,
pubmed-meshheading:8817341-Recombinant Fusion Proteins,
pubmed-meshheading:8817341-Transfection,
pubmed-meshheading:8817341-Tyrosine 3-Monooxygenase
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
Recessively inherited L-DOPA-responsive parkinsonism in infancy caused by a point mutation (L205P) in the tyrosine hydroxylase gene.
|
| pubmed:affiliation |
University Children's Hospital, Bochum, Germany.
|
| pubmed:publicationType |
Journal Article,
Case Reports,
Research Support, Non-U.S. Gov't
|