Interruptions in the expanded ATTCT repeat of spinocerebellar ataxia type 10: Repeat purity as a disease modifier?
Interruptions in the expanded ATTCT repeat of spinocerebellar ataxia type 10: Repeat purity as a disease modifier?
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DOI：
10.1086/498654
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发表时间：
2006-01-01
影响因子：
9.8
通讯作者：
Nelson, DL
中科院分区：
文献类型：
--
作者：
Matsuura, T;Fang, P;Nelson, DL
脊髓小脑性共济失调10型（SCA10）是由简单重复扩增引起的众多遗传性疾病之一。SCA10是由内含子ATTCT五核苷酸重复链扩增引起的。它的临床特征是进行性共济失调、癫痫发作和预期，在家庭内部和家庭之间可能有所不同。我们报告了两个SCA10家族表现出不同的癫痫发作频率和重复长度与发病年龄的相关性。一个家族表现出不间断的ATTCT扩展，而另一个家族则表现出重复序列的多次中断，这些重复序列的长度和/或序列不同。致病的微卫星扩展被认为是由不间断的纯重复序列组成的。我们对SCA10的研究结果挑战了这一惯例，并提示扩增重复元件的纯度可能是一种疾病调节剂。
Spinocerebellar ataxia type 10 ( SCA10) is one of numerous genetic disorders that result from simple repeat expansions. SCA10 is caused by expansion of an intronic ATTCT pentanucleotide repeat tract. It is clinically characterized by progressive ataxia, seizures, and anticipation, which can vary within and between families. We report two SCA10 families showing distinct frequencies of seizures and correlations of repeat length with age at onset. One family displayed uninterrupted ATTCT expansions, whereas the other showed multiple interruptions of the repeat by nonconsensus repeat units, which differed both in the length and/ or sequence of the repeat unit. Disease-causing microsatellite expansions have been assumed to be composed of uninterrupted pure repeats. Our findings for SCA10 challenge this convention and suggest that the purity of the expanded repeat element may be a disease modifier.