A common point mutation in the tyrosine hydroxylase gene in autosomal recessive L-DOPA-responsive dystonia in the Dutch population.
This report concerns one new mutation in the tyrosine hydroxylase (TH) gene in three patients originating from three unrelated Dutch families with autosomal recessive L-DOPA-responsive dystonia (DRD). In this study, all exons of the TH gene were amplified by the polymerase chain reaction and subjected to analyses by single-strand conformation polymorphism. An aberrant migration pattern was observed for exon 6 of the TH gene in all patients. Direct sequencing of the coding region of exon 6 revealed the presence of one novel missense mutation. An a698g transition resulted in the substitution of the evolutionary conserved arginine 233 by a histidine (R233H). All patients were homozygous for the mutation. This new mutation in the TH gene was confirmed by restriction enzyme analysis with the restriction enzyme HhaI. Thus, a high proportion of defective TH alleles may be R233H in The Netherlands.
Laboratory of Pediatrics and Neurology, University Hospital Nijmegen, The Netherlands. B.vandeHeuvel@ckslkn.azn.nl
L P
LP
van den Heuvel
B
B
Luiten
J A
JA
Smeitink
J F
JF
de Rijk-van Andel
K
K
Hyland
G C
GC
Steenbergen-Spanjers
R J
RJ
Janssen
R A
RA
Wevers
D002880:Chromosomes, Human, Pair 11; D003718:Denmark; D004421:Dystonia / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D005808:Genes, Recessive; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase