𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Molecular chaperones affect GTP cyclohydrolase I mutations in dopa-responsive dystonia

✍ Scribed by Wuh-Liang Hwu; Mei-Yi Lu; Kuo-Yuan Hwa; Shu-Wen Fan; Yu-May Lee

Publisher
John Wiley and Sons
Year
2004
Tongue
English
Weight
154 KB
Volume
55
Category
Article
ISSN
0364-5134

No coin nor oath required. For personal study only.

✦ Synopsis

Unstable GTP cyclohydrolase I (GCH) mutations in dopa-responsive dystonia (DRD) can exert a dominant-negative effect in the HeLa cell model, but in a batch of cells this effect could not be shown. Through differential display, we found a higher Hsc70 expression in the non-dominant-negative cells. We further demonstrated that ectopic expression of Hsp40/Hsp70 stabilized the GCH mutant G201E. Moreover, Hsp90 inhibitor geldanamycin destroyed the wild-type GCH level, and heat shock increased the synthesis of GCH protein. Therefore, the dominant-negative effect produced by unstable proteins would be susceptible to the status of molecular chaperones, which could be the modifying genes and therapeutic targets for DRD and other genetic diseases.

πŸ“œ SIMILAR VOLUMES

Dominant negative effect of GTP cyclohyd
Dominant negative effect of GTP cyclohydrolase I mutations in dopa-responsive hereditary progressive dystonia
✍ Makito Hirano; Takehiko Yanagihara; Dr. Satoshi Ueno πŸ“‚ Article πŸ“… 1998 πŸ› John Wiley and Sons 🌐 English βš– 945 KB

Hereditary progressive dystonia (HPD) is caused by the mutant gene encoding GTP cyclohydrolase I (GCH). The clinical presentation of this disease varies considerably, and many cases appear to be sporadic. We have previously proposed that this clinical variation may be due to digetential expression o

Dopa-responsive dystonia and early-onset
Dopa-responsive dystonia and early-onset Parkinson's disease in a patient with GTP cyclohydrolase I deficiency?
✍ Lena Elisabeth Hjermind; Lis Gitte Johannsen; Nenad Blau; Ron Allan Wevers; Chri πŸ“‚ Article πŸ“… 2006 πŸ› John Wiley and Sons 🌐 English βš– 94 KB

We describe a patient with a combination of dystonic and parkinsonian signs. Paraclinical studies revealed a mutation in the GTP cyclohydrolase I gene (GCH1) and a decrease in [ 123 I]-N--fluoropropyl-2␀-carbomethoxy-3␀-(4iodophenyl) nortropane ( 123 I-FP-CIT) binding ratios indicative of Parkinson'

Dystonia with motor delay in compound he
Dystonia with motor delay in compound heterozygotes for GTP-cyclohydrolase I gene mutations
✍ Yoshiaki Furukawa; Stephen J. Kish; E. Martina Bebin; Richard D. Jacobson; Julie πŸ“‚ Article πŸ“… 1998 πŸ› John Wiley and Sons 🌐 English βš– 703 KB

Mutations in the GTP-cyclohydrolase I (GCH) gene have been identified as a cause of two disorders: autosomal dominant hereditary progressive dystonia/dopa-responsive dystonia (HPD/DRD) and autosomal recessive GCH-deficient hyperphenylalaninemia (HPA). Detailed clinical descriptions and genetic analy

Wide expressivity variation and high but
Wide expressivity variation and high but no gender-related penetrance in two dopa-responsive dystonia families with a novel GCH-I mutation
✍ Antonino Uncini; Maria Vittoria De Angelis; Patrizia Di Fulvio; Michele Ragno; G πŸ“‚ Article πŸ“… 2004 πŸ› John Wiley and Sons 🌐 English βš– 102 KB

## Abstract We describe the clinical and molecular correlates in two Italian families with dopa‐responsive dystonia (DRD) and the same novel mutation of GTP‐cyclohydrolase I (GCH‐I) gene. Thirty‐five subjects were examined and the genotype correlated to phenotype. Childhood onset foot dystonia is p