A mutation in the RNF170 gene causes autosomal dominant sensory ataxia

作者：Valdmanis Paul N; Dupre Nicolas; Lachance Mathieu; Stochmanski Shawn J; Belzil Veronique V; Dion Patrick A; Thiffault Isabelle; Brais Bernard; Weston Lyle; Saint Amant Louis; Samuels Mark E; Rouleau Guy A^*

来源：Brain, 2011, 134: 602-607.

DOI：10.1093/brain/awq329

• ataxia
• sensory neuropathy
• gene identification
• ring-finger protein
• RNF170

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.

• 出版日期2011-2