Tandem duplication within the DMD gene in Labrador retrievers with a mild clinical phenotype.
Tandem duplication within the DMD gene in Labrador retrievers with a mild clinical phenotype.
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DOI：
10.1016/j.nmd.2022.08.001
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发表时间：
2022-10
影响因子：
2.8
通讯作者：
Mickelson, James R.
中科院分区：
文献类型：
--
作者：
Shelton, G. Diane;Minor, Katie M.;Vieira, Natassia M.;Kunkel, Louis M.;Friedenberg, Steven G.;Cullen, Jonah N.;Guo, Ling T.;Zatz, Mayana;Mickelson, James R.
一种形式的肌营养不良症与轻度或亚临床神经肌肉的迹象，以前曾报告在一个家庭的拉布拉多寻回犬。在6个月龄时首次发现肌酸激酶活性显著且持续升高。骨骼肌活检显示营养不良的表型，与肌营养不良蛋白检测不到蛋白质印迹和免疫组化染色，并与肌营养不良蛋白的表达增加。在这份报告中，我们证明了蛋白质印迹法，α-肌营养不良蛋白聚糖是在基本上正常的水平。全基因组测序现在也揭示了约400 kb的串联基因组DNA重复，包括插入野生型基因内含子7的DMD基因的外显子2-7。来自2例病例的骨骼肌cDNA含有DMD转录物，正如预期的那样，来自框内正确剪接的外显子2-7串联插入。在一个患有扩张型心肌病但没有骨骼肌病的人类家族中，已经报道了涉及DMD外显子2-7的类似5'重复。这是拉布拉多猎犬DMD基因中第3次被证实的突变。
A form of dystrophinopathy with mild or subclinical neuromuscular signs has been previously reported in a family of Labrador retrievers. Markedly and persistently elevated creatine kinase activity was first noted at 6 months of age. Skeletal muscle biopsies revealed a dystrophic phenotype, with dystrophin non-detectable on western blotting and immunohistochemical staining, and with increased utrophin expression. In this report we demonstrate with western blotting that α-dystroglycan is present at essentially normal levels. Whole genome sequencing has also now revealed an approximately 400kb tandem genomic DNA duplication including exons 2-7 of the DMD gene that was inserted into intron 7 of the wild type gene. Skeletal muscle cDNA from 2 cases contained DMD transcripts as expected from an in-frame properly-spliced exon 2-7 tandem insertion. A similar 5’ duplication involving DMD exons 2-7 has been reported in a human family with dilated cardiomyopathy but without skeletal myopathy. This is the 3rd confirmed mutation in the DMD gene in Labrador retrievers.
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影响因子：
11.2
作者：
Flanigan, Kevin M.;Ceco, Ermelinda;Lamar, Kay-Marie;Kaminoh, Yuuki;Dunn, Diane M.;Mendell, Jerry R.;King, Wendy M.;Pestronk, Alan;Florence, Julaine M.;Mathews, Katherine D.;Finkel, Richard S.;Swoboda, Kathryn J.;Gappmaier, Eduard;Howard, Michael T.;Day, John W.;McDonald, Craig;McNally, Elizabeth M.;Weiss, Robert B.
通讯作者：
Weiss, Robert B.
DOI：
10.1073/pnas.1001517107
发表时间：
2010-05-25
影响因子：
11.1
作者：
Henderson, Davin M.;Lee, Ann;Ervasti, James M.
通讯作者：
Ervasti, James M.
影响因子：
3.4
作者：
Hakim, Chady H.;Duan, Dongsheng
通讯作者：
Duan, Dongsheng
影响因子：
4
作者：
BERTELSON, CJ;BARTLEY, JA;KUNKEL, LM
通讯作者：
KUNKEL, LM
影响因子：
0.8
作者：
Baroncelli, A. B.;Abellonio, F.;Paciello, O.
通讯作者：
Paciello, O.