Pm. Knappskog et al., RECESSIVELY INHERITED L-DOPA-RESPONSIVE DYSTONIA CAUSED BY A POINT MUTATION (Q381K) IN THE TYROSINE-HYDROXYLASE GENE, Human molecular genetics, 4(7), 1995, pp. 1209-1212
Tyrosine hydroxylase (TH) catalyzes the conversion of L-tyrosine to L-
dihydroxyphenylalanine (L-DOPA), the rate-limiting step in the biosynt
hesis of dopamine, Recently, we described a point mutation in hTH (Q38
1K) in a family of two siblings suffering from progressive L-DOPA-resp
onsive dystonia (DRD), representing the first reported mutation in thi
s gene, We here describe the cloning, expression and steady-state kine
tic properties of the recombinant mutant enzyme, When expressed by a c
oupled in vitro transcription-translation system and in E.coli, the mu
tant enzyme represents a kinetic variant form, with a reduced affinity
for L-tyrosine, The 'residual activity' of about 15% of the correspon
ding wild-type hTH (isoform hTH1), at substrate concentrations prevail
ing in vivo, is compatible with the clinical phenotype of the two Q381
K homozygote patients carrying this recessively inherited mutation.