Anticipation and intergenerational repeat instability in spinocerebellar ataxia type 17.
Anticipation and intergenerational repeat instability in spinocerebellar ataxia type 17.
复制标题
17 型脊髓小脑共济失调的预期和代际重复不稳定性。
DOI：
10.1002/ana.21139
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发表时间：
2007
影响因子：
11.2
通讯作者：
Bidichandani,SanjayI
中科院分区：
文献类型：
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作者：
Rasmussen,Astrid;DeBiase,Irene;Fragoso-Benítez,Marcela;Macías-Flores,MarcoAntonio;Yescas,Petra;Ochoa,Adriana;Ashizawa,Tetsuo;Alonso,MaríaElisa;Bidichandani,SanjayI
脊髓小脑性共济失调 17 型 (SCA17) 是由 TBP 基因中 CAG/CAA 重复序列的扩增引起的。大多数致病等位基因被中断，并在没有预期的情况下稳定地从亲代传播到后代。我们鉴定了三个具有不间断等位基因扩展的 SCA17 家族，从而大大增加了此类等位基因的已知代际传播数量。我们发现不间断的 SCA17 等位基因是不稳定的，与预期相关，并且表现出随着年龄的增长而增加的父系扩张偏差。即使重复长度的微小增量也会导致预期的过度增加。预期也与童年表现有关。有效的遗传咨询需要对所有 SCA17 等位基因进行测序。安·尼罗尔 2007
Spinocerebellar ataxia type 17 (SCA17) is caused by expansion of a CAG/CAA repeat in theTBPgene. Most pathogenic alleles are interrupted and are stably transmitted from parent to offspring without anticipation. We identified three SCA17 families with expansion of uninterrupted alleles, thus greatly increasing the number of known intergenerational transmissions of such alleles. We found that uninterrupted SCA17 alleles are unstable, associated with anticipation, and show a paternal expansion bias that increases with age. Even small increments in repeat length resulted in inordinate increases in anticipation. Anticipation was also associated with childhood presentation. Sequencing of all SCA17 alleles is required for effective genetic counseling. Ann Neurol 2007