Nonsense mutation-associated Becker muscular dystrophy: interplay between exon definition and splicing regulatory elements within the DMD gene.
Nonsense mutation-associated Becker muscular dystrophy: interplay between exon definition and splicing regulatory elements within the DMD gene.
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DOI：
10.1002/humu.21426
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发表时间：
2011-03
期刊：
影响因子：
3.9
通讯作者：
Weiss, Robert B.
中科院分区：
文献类型：
--
作者：
Flanigan, Kevin M.;Dunn, Diane M.;von Niederhausern, Andrew;Soltanzadeh, Payam;Howard, Michael T.;Sampson, Jacinda B.;Swoboda, Kathryn J.;Bromberg, Mark B.;Mendell, Jerry R.;Taylor, Laura E.;Anderson, Christine B.;Pestronk, Alan;Florence, Julaine M.;Connolly, Anne M.;Mathews, Katherine D.;Wong, Brenda;Finkel, Richard S.;Bonnemann, Carsten G.;Day, John W.;McDonald, Craig;Weiss, Robert B.
由于蛋白质翻译的过早终止，通常预测无义突变作为无效等位基因起作用。然而，编码肌营养不良蛋白的DMD基因中的无义突变与严重的杜氏肌营养不良症（DMD）和较轻的贝克尔肌营养不良症（BMD）表型都相关。在一项大型调查中，我们在DMD基因中鉴定了243个独特的无义突变，其中210个我们可以建立明确的表型。我们分析了由发现无义突变的外显子侧翼预测的阅读框架，并提出证据表明无义突变导致BMD可能通过诱导外显子跳跃来实现，证实影响外显子定义的外显子点突变在确定表型中发挥了重要作用。我们提出了一个新的模型的基础上的组合的外显子定义和内含子剪接调控元件的BMD无义突变的选择性协会与一个子集的DMD外显子容易突变诱导的外显子跳跃。
Nonsense mutations are usually predicted to function as null alleles due to premature termination of protein translation. However, nonsense mutations in the DMD gene, encoding the dystrophin protein, have been associated with both the severe Duchenne Muscular Dystrophy (DMD) and milder Becker Muscular Dystrophy (BMD) phenotypes. In a large survey, we identified 243 unique nonsense mutations in the DMD gene, and for 210 of these we could establish definitive phenotypes. We analyzed the reading frame predicted by exons flanking those in which nonsense mutations were found, and present evidence that nonsense mutations resulting in BMD likely do so by inducing exon skipping, confirming that exonic point mutations affecting exon definition have played a significant role in determining phenotype. We present a new model based on the combination of exon definition and intronic splicing regulatory elements for the selective association of BMD nonsense mutations with a subset of DMD exons prone to mutation-induced exon skipping.
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影响因子：
2.8
作者：
Flanigan, Kevin M.;Dunn, Diane M.;Weiss, Robert B.
通讯作者：
Weiss, Robert B.
影响因子：
3.9
作者：
Gurvich, Olga L.;Maiti, Baijayanta;Flanigan, Kevin M.
通讯作者：
Flanigan, Kevin M.
影响因子：
14.9
作者：
Desmet FO;Hamroun D;Lalande M;Collod-Béroud G;Claustres M;Béroud C
通讯作者：
Béroud C
影响因子：
2
作者：
Dent, KM;Dunn, DM;Flanigan, KM
通讯作者：
Flanigan, KM
影响因子：
30.8
作者：
Cartegni, L;Krainer, AR
通讯作者：
Krainer, AR