 |
|
The GTP Cyclohydrolase I Gene in Russian Families With Dopa-Responsive Dystonia
Sergei N. Illarioshkin, MD;
Elena D. Markova, MD;
Pyotr A. Slominsky, PhD;
Natalya I. Miklina, MD;
Svetlana N. Popova, PhD;
Svetlana A. Limborska, PhD;
Shoji Tsuji, MD;
Irina A. Ivanova-Smolenskaya, MD
Arch Neurol. 1998;55:789-792.
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 patients with sporadic DRD were examined. Mutation screening was performed using single-strand conformation polymorphism analysis followed by direct sequencing of the presumably mutated exons; in patients whose results showed a normal pattern on single-strand conformation polymorphism 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 autosomal-dominant inheritance. All these mutations are predicted to cause amino acid changes in the highly conserved regions of the gene. In patients 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 account for a significant fraction (up to half) of the patients with a typical clinical picture of DRD. None of the mutations in the GCH-I gene described so far were detected more than once, which precludes the possibility of creating simple DNA testing procedures for routine clinical practice.
From the Department of Neurogenetics, Institute of Neurology, Russian Academy of Medical Sciences (Drs Illarioshkin, Markova, Miklina, and Ivanova-Smolenskaya), and the Department of Molecular Basis of Human Genetics, Institute of Molecular Genetics, Russian Academy of Sciences (Drs Slominsky, Popova, and Limborska), Moscow, Russia; and the Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan (Dr Tsuji).
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Levodopa-responsive dystonia: GTP cyclohydrolase I or parkin mutations?
Tassin et al.
Brain 2000;123:1112-1121.
ABSTRACT
| FULL TEXT
|
