11 August 2020
Protein defect points to new ataxia
Published online 7 September 2010
Over the past two decades, several genetic mechanisms have been identified for different types of ataxias, a neurological disorder of both the central and peripheral nervous system. These range from mutations in genes that code for mitochondrial proteins to ones that play a role in DNA repair.
A team of Saudi Arabian and French researchers have identified an unknown form of recessive ataxia, a hereditary form of ataxia, which they dub "Salih ataxia", in three Saudi Arabian children from a large consanguineous family.
The researchers found that this form of ataxia is caused by a mutation in the gene KIAA0226, which codes the novel protein rundataxin. The three children's parents and healthy carriers of a single mutated gene showed no signs or symptoms of ataxia, eliminating the possibility that the mutation could be dominant. The frameshift mutation in the gene alters the tail end of rundataxin, causing only a partial loss of protein function.
The disease onsets early in childhood, progressing to pure cerebellar ataxia into the teenage years. Two of the three children also showed epilepsy and mental retardation, but with such a small sample size it remains inconclusive whether these conditions are related to the mutation in the rundataxin gene.
Deficiency of this newly found protein appears to cause ataxia through vesicular trafficking and cellular signalling pathways unlike known forms. Its function and role inside the body is still unknown, but further study of rundataxin and its structure should shed light on how this defective protein can cause ataxia.
- Assoum, M. & Salih, M. et al. Rundataxin, a novel protein with RUN and diacylglycerol binding domains, is mutant in a new recessive ataxia. Brain. 133, 2439-2447 (2010) | PubMed |