Sn. Illarioshkin et al., THE GTP CYCLOHYDROLASE-I GENE IN RUSSIAN FAMILIES WITH DOPA-RESPONSIVE DYSTONIA, Archives of neurology, 55(6), 1998, pp. 789-792
Objective: To search for mutations in the GTP cyclohydrolase I (GCH-I)
gene in a set of Russian families with dopa-responsive dystonia (DRD)
. Design: Six large families with 54 affected family members and 2 pat
ients with sporadic DRD were examined. Mutation screening was performe
d using single-strand conformation polymorphism analysis followed by d
irect sequencing of the presumably mutated exons; in patients whose re
sults showed a normal pattern on single-strand conformation polymorphi
sm analysis, the entire coding region of the GCH-I gene was sequenced.
Results: Three new heterozygote point mutations located within exons
1, 2, and 4 of the GCH-I gene were identified in 3 families with autos
omal-dominant inheritance. All these mutations are predicted to cause
amino acid changes in the highly conserved regions of the gene. In pat
ients from 3 other families and in both patients with sporadic DRD, no
alterations in the translated portion of the GCH-I gene were observed
. Conclusions: Mutations in the coding region of the GCH-I gene accoun
t for a significant fraction (up to half) of the patients with a typic
al clinical picture of DRD. None of the mutations in the GCH-I gene de
scribed so far were detected more than once, which precludes the possi
bility of creating simple DNA testing procedures for routine clinical
practice.