THE GTP CYCLOHYDROLASE-I GENE IN RUSSIAN FAMILIES WITH DOPA-RESPONSIVE DYSTONIA

Citation
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
Citations number
25
Categorie Soggetti
Clinical Neurology
Journal title
ISSN journal
00039942
Volume
55
Issue
6
Year of publication
1998
Pages
789 - 792
Database
ISI
SICI code
0003-9942(1998)55:6<789:TGCGIR>2.0.ZU;2-D
Abstract
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.