Recessively inherited L-DOPA-responsive dystonia caused by a point mutation (Q381K) in the tyrosine hydroxylase gene.
Article Details
- CitationCopy to clipboard
Knappskog PM, Flatmark T, Mallet J, Ludecke B, Bartholome K
Recessively inherited L-DOPA-responsive dystonia caused by a point mutation (Q381K) in the tyrosine hydroxylase gene.
Hum Mol Genet. 1995 Jul;4(7):1209-12.
- PubMed ID
- 8528210 [ View in PubMed]
- Abstract
Tyrosine hydroxylase (TH) catalyzes the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-DOPA), the rate-limiting step in the biosynthesis of dopamine. Recently, we described a point mutation in hTH (Q381K) in a family of two siblings suffering from progressive L-DOPA-responsive dystonia (DRD), representing the first reported mutation in this gene. We here describe the cloning, expression and steady-state kinetic properties of the recombinant mutant enzyme. When expressed by a coupled in vitro transcription-translation system and in E. coli, the mutant enzyme represents a kinetic variant form, with a reduced affinity for L-tyrosine. The 'residual activity' of about 15% of the corresponding wild-type hTH (isoform hTH1), at substrate concentrations prevailing in vivo, is compatible with the clinical phenotype of the two Q381K homozygote patients carrying this recessively inherited mutation.