Molecular basis of spinocerebellar ataxias subtype caused by nucleotide repeat expansion in noncoding region

Hereditary spinocerebellar ataxias(SCA)are mainly caused by trinucleotide(CAG/CAA)repeat expansion in open reading frames of corresponding gene.However,SCA8,SCAIO and SCAl2 are caused by nucleotide repeat expansion in noncoding region.Recent researches focus on the pathogenesis and hereditary traits,including the in stability of nucleotide repeat,the alteration of penetrance,the bias of gender inheritance and the anticipation.Tile patho genesis of these three SCA subtypes is different from other subtypes because the repeat expansion in noncoding region has mild influence on translation of polyQ protein.We suggest that the interference Oil DNA transcription by the abnormal nucleotide expansiOn,the post-transcriptional toxic effect of abnormal RNA,and the mechanism of bidirectional expression of repeat expansion transcripts play a critical role Oil SCA8,SCAl0 and SCAl2 pathogenesis. Key words: spinocerebellar ataxias;  nucleotide repeat;  nonpenetrance;  pathogenesy;  bidirectional trail.scription