Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures.
Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures.
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DOI：
10.1007/s10048-013-0385-6
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发表时间：
2014-03
期刊：
影响因子：
2.2
通讯作者：
Ashizawa, Tetsuo
中科院分区：
文献类型：
--
作者：
McFarland, Karen N.;Liu, Jilin;Landrian, Ivette;Zeng, Desmond;Raskin, Salmo;Moscovich, Mariana;Gatto, Emilia M.;Ochoa, Adriana;Teive, Helio A. G.;Rasmussen, Astrid;Ashizawa, Tetsuo
关键词：
脊髓小脑性共济失调10型（SCA 10）是一种常染色体显性遗传性神经退行性疾病，是Ataxin 10基因内含子9内非编码五核苷酸重复扩增的结果。SCA 10患者表现为单纯的小脑共济失调;然而，一些家族也有很高的癫痫发病率。含有五核苷酸和七核苷酸中断基序的SCA 10扩增，称为“ATCCT中断”，在种系传播期间经历大的收缩，特别是在父系谱系中。与此同时，这些等位基因赋予了更早的发病年龄，这与重复扩增中遗传预测的传统规则相矛盾。此前，ATCCT中断与一个墨西哥裔美国SCA 10家族中癫痫发作的患病率较高相关。在一个SCA 10家族的大队列中，我们分析了ATCCT中断是否会增加这些家族癫痫发作的风险。值得注意的是，我们发现SCA 10扩展中重复中断的存在使SCA 10患者发生癫痫的风险增加6.3倍（仅考虑墨西哥血统患者时为6.2倍），并且具有阳性癫痫家族史的风险增加13.7倍（仅考虑墨西哥血统患者时为10.5倍）。我们的结论是，SCA 10重复扩增的重复中断的存在表明癫痫表型的显着风险，并应考虑在遗传咨询。
Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant neurodegenerative disorder, is the result of a non-coding, pentanucleotide repeat expansion within intron 9 of the Ataxin 10 gene. SCA10 patients present with pure cerebellar ataxia; yet, some families also have a high incidence of epilepsy. SCA10 expansions containing penta- and heptanucleotide interruption motifs, termed “ATCCT interruptions,” experience large contractions during germline transmission, particularly in paternal lineages. At the same time, these alleles confer an earlier age at onset which contradicts traditional rules of genetic anticipation in repeat expansions. Previously, ATCCT interruptions have been associated with a higher prevalence of epileptic seizures in one Mexican-American SCA10 family. In a large cohort of SCA10 families, we analyzed whether ATCCT interruptions confers a greater risk for developing seizures in these families. Notably, we find that the presence of repeat interruptions within the SCA10 expansion confers a 6.3-fold increase in the risk of an SCA10 patient developing epilepsy (6.2-fold when considering patients of Mexican ancestry only) and a 13.7-fold increase in having a positive family history of epilepsy (10.5-fold when considering patients of Mexican ancestry only). We conclude that the presence of repeat interruptions in SCA10 repeat expansion indicates a significant risk for the epilepsy phenotype and should be considered during genetic counseling.
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影响因子：
9.9
作者：
Wakamiya, M.;Matsuura, T.;Ashizawa, T.
通讯作者：
Ashizawa, T.
影响因子：
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影响因子：
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通讯作者：
Brusco, A
影响因子：
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作者：
QUAN, F;JANAS, J;POPOVICH, BW
通讯作者：
POPOVICH, BW
影响因子：
2.2
作者：
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通讯作者：
Matsumoto, Naomichi