Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9
Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9
复制标题
DOI：
10.1126/science.1062125
复制
发表时间：
2001-08-03
期刊：
影响因子：
56.9
通讯作者：
Ranum, LPW
中科院分区：
文献类型：
--
作者：
Liquori, CL;Ricker, K;Ranum, LPW
肌强直性营养不良（DM）是成人中最常见的肌肉营养不良形式，可由染色体19q13 （DM1）或3q21 （DM2/PROMM）突变引起。DM1是由营养不良肌强直蛋白激酶基因（DMPK） 3'非翻译区CTG扩增引起的。有几种机制被用来解释这种不改变基因蛋白质编码部分的突变如何导致DM的特定临床特征。我们现在报道DM2是由锌指蛋白9 （ZNF9）基因内含子1上的CCTG扩增引起的（平均相似于5000次重复）。这些突变之间的相似性表明，RNA中的微卫星扩增可能具有致病性，并导致DM1和DM2的多系统特征。
Myotonic dystrophy (DM), the most common form of muscular dystrophy in adults, can be caused by a mutation on either chromosome 19q13 (DM1) or 3q21 (DM2/PROMM). DM1 is caused by a CTG expansion in the 3' untranslated region of the dystrophia myotonica-protein kinase gene (DMPK). Several mechanisms have been invoked to explain how this mutation, which does not alter the protein-coding portion of a gene, causes the specific constellation of clinical features characteristic of DM. We now report that DM2 is caused by a CCTG expansion (mean similar to 5000 repeats) located in intron 1 of the zinc finger protein 9 (ZNF9) gene. Parallels between these mutations indicate that microsatellite expansions in RNA can be pathogenic and cause the multisystemic features of DM1 and DM2.