Mutations in SYNE1 lead to a newly discovered form of autosomal recessive cerebellar ataxia
Mutations in SYNE1 lead to a newly discovered form of autosomal recessive cerebellar ataxia
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DOI：
10.1038/ng1927
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发表时间：
2007-01-01
期刊：
影响因子：
30.8
通讯作者：
Rouleau, Guy A.
中科院分区：
文献类型：
--
作者：
Gros-Louis, Francois;Dupre, Nicolas;Rouleau, Guy A.
过去十年来，在揭示遗传性共济失调的生物学基础方面取得了巨大进展。脊髓小脑共济失调（SCA）的分子研究扩展了我们对显性共济失调的理解(1)。已经确定了一些常染色体隐性共济失调的致病基因：弗里德赖希共济失调(2)，共济失调伴维生素E缺乏(3)，共济失调毛细血管扩张(4)，隐性痉挛性共济失调的Charlevoix-Saguenay(5)和共济失调伴动眼运动失用1型（参考文献）。6,7)和类型2（参考文献8）。尽管如此，大多数隐性共济失调的基因仍未确定。此外，纯小脑共济失调，占所有共济失调的20%，研究仍然很少，只有两个致病显性基因被描述：CACNA1A（参考文献9）和SPTBN2（参考文献10）。在这里，我们报告了一种新发现的隐性共济失调形式，并表明SYNE1突变在我们所有的亲属中都是致病的，使SYNE1成为第一个被发现的隐性遗传的纯小脑性共济失调的基因。
The past decade has seen great advances in unraveling the biological basis of hereditary ataxias. Molecular studies of spinocerebellar ataxias (SCA) have extended our understanding of dominant ataxias(1). Causative genes have been identified for a few autosomal recessive ataxias: Friedreich's ataxia(2), ataxia with vitamin E deficiency(3), ataxia telangiectasia(4), recessive spastic ataxia of Charlevoix-Saguenay(5) and ataxia with oculomotor apraxia type 1 (refs. 6,7) and type 2 (ref. 8). Nonetheless, genes remain unidentified for most recessive ataxias. Additionally, pure cerebellar ataxias, which represent up to 20% of all ataxias, remain poorly studied with only two causative dominant genes being described: CACNA1A (ref. 9) and SPTBN2 (ref. 10). Here, we report a newly discovered form of recessive ataxia in a French-Canadian cohort and show that SYNE1 mutations are causative in all of our kindreds, making SYNE1 the first identified gene responsible for a recessively inherited pure cerebellar ataxia.