【佳學(xué)基因靶向藥物基因檢測(cè)】Slc9a6 突變導(dǎo)致?lián)u床大鼠浦肯野細(xì)胞丟失和共濟(jì)失調(diào)

基因腫瘤檢測(cè)費(fèi)17800說(shuō)明

開(kāi)會(huì)學(xué)習(xí)醫(yī)學(xué)博士年度報(bào)告表《基因組織易感位點(diǎn)列表及發(fā)生率分析》《Hum Mol Genet》在?2023 Jan 9;ddad004.發(fā)表了一篇題目為《》腫瘤靶向藥物治療基因檢測(cè)臨床研究文章。該研究由Karla P Figueroa,?Collin J Anderson,?Sharan Paul,?Warunee Dansithong,?Mandi Gandelman,?Daniel R Scoles,?Stefan M Pulst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。

腫瘤基因檢測(cè)及靶向藥物治療研究關(guān)鍵詞：

進(jìn)行性,共濟(jì)失調(diào),浦肯野細(xì)胞,Slc9a6

腫瘤治療檢測(cè)基因臨床應(yīng)用結(jié)果

搖床大鼠攜帶自然發(fā)生的突變，導(dǎo)致進(jìn)行性共濟(jì)失調(diào)，其特征是浦肯野細(xì)胞 (PC) 丟失。我們之前曾報(bào)道過(guò)將搖床軌跡精細(xì)映射到大鼠 X 染色體的長(zhǎng)臂。在這項(xiàng)工作中，我們?cè)噲D確定振動(dòng)器表型背后的突變基因，并通過(guò)功能互補(bǔ)確認(rèn)其身份。我們對(duì)候選區(qū)域進(jìn)行了精細(xì)定位并分析了小腦轉(zhuǎn)錄組，確定了與疾病分離的 Slc9a6 基因中的 XM_217630.9 (Slc9a6):c.[191_195delinsA] 變體。我們使用小鼠 L7-6 (L7) 啟動(dòng)子生成了一種將 Slc9a6 表達(dá)靶向 PC 的腺相關(guān)病毒 (AAV)。我們通過(guò)腦室內(nèi)注射在 PC 變性開(kāi)始之前管理 AAV，發(fā)現(xiàn)它減少了振動(dòng)器電機(jī)、分子和細(xì)胞表型。因此，Slc9a6 在搖床中發(fā)生突變，基于 AAV 的基因治療可能是同樣由 Slc9a6 突變引起的 Christianson 綜合征的可行治療策略。

腫瘤發(fā)生與革命國(guó)際數(shù)據(jù)庫(kù)描述：

The shaker rat carries a naturally occurring mutation leading to progressive ataxia characterized by Purkinje cell (PC) loss. We previously reported on fine-mapping the shaker locus to the long arm of the rat X chromosome. In this work, we sought to identify the mutated gene underlying the shaker phenotype and confirm its identity by functional complementation. We fine-mapped the candidate region and analyzed cerebellar transcriptomes, identifying a XM_217630.9 (Slc9a6):c.[191_195delinsA] variant in the Slc9a6 gene that segregated with disease. We generated an adeno-associated virus (AAV) targeting Slc9a6 expression to PCs using the mouse L7-6 (L7) promoter. We administered the AAV prior to the onset of PC degeneration through intracerebroventricular injection and found that it reduced the shaker motor, molecular, and cellular phenotypes. Therefore, Slc9a6 is mutated in shaker and AAV-based gene therapy may be a viable therapeutic strategy for Christianson syndrome, also caused by Slc9a6 mutation.