【佳學(xué)基因檢測(cè)】反復(fù)性 COL6A1 假外顯子插入會(huì)導(dǎo)致肌營(yíng)養(yǎng)不良,并且是剪接校正療法的有效目標(biāo)
如何知道小孩是否有基因突變?cè)u(píng)價(jià)
探索腫瘤的基因組學(xué)特征與治療方案設(shè)計(jì)體會(huì)到《Nature》在2017 Apr 26; 545(7655): 446–451.發(fā)表了一篇題目為《反復(fù)性 COL6A1 假外顯子插入會(huì)導(dǎo)致肌營(yíng)養(yǎng)不良,并且是剪接校正療法的有效目標(biāo)》腫瘤靶向藥物治療基因檢測(cè)臨床研究文章。該研究由Christopher Abbosh, Nicolai J. Birkbak, Gareth A. Wilson, Mariam Jamal-Hanjani, Tudor Constantin, Raheleh Salari, John Le Quesne, David A Moore,+ Selvaraju Veeriah,+ Rachel Rosenthal, Teresa Marafioti, Eser Kirkizlar, Thomas B K Watkins, Nicholas McGranahan, Sophia Ward, Luke Martinson, Joan Riley, Francesco Fraioli, Maise Al Bakir, Eva Gr?nroos, Francisco Zambrana, Raymondo Endozo, Wenya Linda Bi, Fiona M. Fennessy, Nicole Sponer, Diana Johnson, Joanne Laycock, Seema Shafi, Justyna Czyzewska-Khan, Andrew Rowan, Tim Chambers, Nik Matthews, Samra Turajlic, Crispin Hiley, Siow Ming Lee, Martin D. Forster, Tanya Ahmad, Mary Falzon, Elaine Borg, David Lawrence, Martin Hayward, Shyam Kolvekar, Nikolaos Panagiotopoulos, Sam M Janes, Ricky Thakrar, Asia Ahmed, Fiona Blackhall, Yvonne Summers, Dina Hafez, Ashwini Naik, Apratim Ganguly, Stephanie Kareht, Rajesh Shah, Leena Joseph, Anne Marie Quinn, Phil Crosbie, Babu Naidu, Gary Middleton, Gerald Langman, Simon Trotter, Marianne Nicolson, Hardy Remmen, Keith Kerr, Mahendran Chetty, Lesley Gomersall, Dean Fennell, Apostolos Nakas, Sridhar Rathinam, Girija Anand, Sajid Khan, Peter Russell, Veni Ezhil, Babikir Ismail, Melanie Irvin-sellers, Vineet Prakash, Jason Lester, Malgorzata Kornaszewska, Richard Attanoos, Haydn Adams, Helen Davies, Dahmane Oukrif, Ayse U Akarca, John A Hartley, Helen L Lowe, Sara Lock, Natasha Iles, Harriet Bell, Yenting Ngai, Greg Elgar, Zoltan Szallasi, Roland F Schwarz, Javier Herrero, Aengus Stewart, Sergio A Quezada, Karl S. Peggs, Peter Van Loo, Caroline Dive, Jimmy Lin, Matthew Rabinowitz, Hugo JWL Aerts, Allan Hackshaw, Jacqui A Shaw, Bernhard G. Zimmermann, and Charles Swanton, on behalf of the TRACERx and PEACE consortia等完成。促進(jìn)了腫瘤的正確治療與個(gè)性化用藥的發(fā)展,進(jìn)一步強(qiáng)調(diào)了基因信息檢測(cè)與分析的重要性。
腫瘤靶向藥物及正確治療臨床研究?jī)?nèi)容關(guān)鍵詞:
肌肉生物學(xué),治療學(xué),膠原蛋白,細(xì)胞外基質(zhì),神經(jīng)肌肉疾病
腫瘤靶向治療基因檢測(cè)臨床應(yīng)用結(jié)果
先進(jìn)的下一代測(cè)序技術(shù)的臨床應(yīng)用越來(lái)越多地揭示了可能作為正確醫(yī)學(xué)治療潛在靶點(diǎn)的新型突變類(lèi)型。在這里,我們展示了 COL6A1 基因中的深層內(nèi)含子剪接缺陷,賊初是通過(guò)對(duì)具有 VI 型膠原相關(guān)營(yíng)養(yǎng)不良 (COL6-RD) 臨床發(fā)現(xiàn)的患者應(yīng)用肌肉 RNA 測(cè)序發(fā)現(xiàn)的,將一個(gè)框內(nèi)假外顯子插入到 COL6A1 mRNA 中,編碼一種突變型膠原蛋白α1(VI)蛋白,對(duì)膠原蛋白VI基質(zhì)組裝產(chǎn)生顯性負(fù)效應(yīng),并為旨在恢復(fù)正?;虮磉_(dá)的剪接校正方法提供了獨(dú)特的機(jī)會(huì)。使用剪接調(diào)節(jié)反義寡聚體,我們有效地跳過(guò)了患者來(lái)源的成纖維細(xì)胞培養(yǎng)物中的假外顯子并恢復(fù)了野生型基質(zhì)。同樣,我們使用 CRISPR/Cas9 正確刪除了包含假外顯子的內(nèi)含子序列,并有效地消除了它的包含,同時(shí)保留了野生型剪接??紤]到這種剪接缺陷正在成為 COL6-RD 中賊常見(jiàn)的突變之一,特異性和有效的剪接校正療法的設(shè)計(jì)為臨床轉(zhuǎn)化提供了一條有希望的途徑。關(guān)鍵詞:肌肉生物學(xué),治療學(xué)關(guān)鍵詞:膠原蛋白,細(xì)胞外基質(zhì),神經(jīng)肌肉疾病
腫瘤發(fā)生與反復(fù)轉(zhuǎn)移國(guó)際數(shù)據(jù)庫(kù)描述:
Muscle Biology, Therapeutics,Collagens, Extracellular matrix, Neuromuscular disease
(責(zé)任編輯:佳學(xué)基因)