PUBLICATION
A mutation in the RNF170 gene causes autosomal dominant sensory ataxia
- Authors
- Valdmanis, P.N., Dupre, N., Lachance, M., Stochmanski, S.J., Belzil, V.V., Dion, P.A., Thiffault, I., Brais, B., Weston, L., Saint-Amant, L., Samuels, M.E., and Rouleau, G.A.
- ID
- ZDB-PUB-101201-45
- Date
- 2011
- Source
- Brain : a journal of neurology 134(Pt 2): 602-607 (Journal)
- Registered Authors
- Saint-Amant, Louis
- Keywords
- ataxia, sensory neuropathy, gene identification, ring-finger protein, RNF170
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Ataxia/genetics*
- Ataxia/metabolism
- Cell Death/drug effects
- DNA Copy Number Variations
- Gene Knockdown Techniques/methods
- Humans
- Mutation, Missense*
- Oligodeoxyribonucleotides, Antisense/pharmacology
- Ubiquitin-Protein Ligases/genetics*
- Ubiquitin-Protein Ligases/metabolism
- Zebrafish
- PubMed
- 21115467 Full text @ Brain
Citation
Valdmanis, P.N., Dupre, N., Lachance, M., Stochmanski, S.J., Belzil, V.V., Dion, P.A., Thiffault, I., Brais, B., Weston, L., Saint-Amant, L., Samuels, M.E., and Rouleau, G.A. (2011) A mutation in the RNF170 gene causes autosomal dominant sensory ataxia. Brain : a journal of neurology. 134(Pt 2):602-607.
Abstract
Autosomal dominant sensory ataxia is a rare genetic condition that results in a progressive ataxia that is caused by degeneration of the posterior columns of the spinal cord. To date only two families have been clinically ascertained with this condition, both from Maritime Canada. We previously mapped both families to chromosome 8p12-8q12 and have now screened the majority of annotated protein-coding genes in the shared haplotype region by direct DNA sequencing. We have identified a putative pathogenic mutation in the gene encoding ring-finger protein RNF170, a potential ubiquitin ligase. This mutation is a rare non-synonymous change in a well-conserved residue and is predicted to be pathogenic by SIFT, PolyPhen, PANTHER and Align-GVD. Microinjection of wild-type or mutant orthologous messenger RNAs into zebrafish (Danio rerio) embryos confirmed that the mutation dominantly disrupts normal embryonic development. Together these results suggest that the mutation in RNF170 is causal for the sensory ataxia in these families.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping