摘要
遗传性脊髓小脑型共济失调(hereditary spinocerebellar ataxias,SCAs)的发病大部分与基因编码区三核苷酸CAG/CAA的异常重复有关,而SCA8、SCA10、SCA12的发病分别与致病基因非编码区CTA/CTG、ATFCT和CAG的异常重复突变有关;近来的研究主要集中在3种亚型的遗传特征和发病机制上面,如核苷酸重复的不稳定性不同外显率的改变、疾病遗传的性别偏倚和遗传早现现象等。由于非编码区核苷酸重复对翻译成多聚谷氨酰胺蛋白的影响不大,3种SCA亚型的发病机制和其它SCAS亚型完全不同,核苷酸的异常重复对DNA转录的干扰、转录后含异常核苷酸重复的RNA的毒性作用以及重复序列不同方向上的双向转录机制在3种SCA亚型的发病机制中可能起到了关键作用。
Hereditary spinocerebellar ataxias(SCA) are mainly caused by trinucleotide (CAG/CAA) repeat expansion in open reading frames of corresponding gene. However, SCA8, SCA10 and SCA12 are caused by nucleotide repeat expansion in noneoding region. Recent researches focus on the pathogenesis and hereditary traits, including the instability of nucleotide repeat, the alteration of penetrance, the bias of gender inheritance and the anticipation. The pathogenesis 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 on DNA transcription by the abnormal nueleotide expansion, the post-transcriptional toxic effect of abnormal RNA, and the mechanism of bidirectional expression of repeat expansion transcripts play a critical role on SCA8, SCA10 and SCA12 pathogenesis.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2008年第3期293-296,共4页
Chinese Journal of Medical Genetics
基金
国家“863”高技术研究发展科题(2004AA227040)
国家自然科学基金(30710303061,30400262)
国家“十五”科技攻关计划课题(2004BA720A03)
关键词
脊髓小脑型共济失调
核苷酸重复
外显不全
发病机制
双向转录
spinocerebellar ataxias
nucleotide repeat
nonpenetrance
pathogenesy
bidirectional transcription