【佳學基因靶向藥物基因檢測】Slc9a6 突變導致?lián)u床大鼠浦肯野細胞丟失和共濟失調(diào)

基因腫瘤檢測費17800說明

開會學習醫(yī)學博士年度報告表《基因組織易感位點列表及發(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。促進了腫瘤的正確治療與個性化用藥的發(fā)展，進一步強調(diào)了基因信息檢測與分析的重要性。

腫瘤基因檢測及靶向藥物治療研究關鍵詞：

進行性,共濟失調(diào),浦肯野細胞,Slc9a6

腫瘤治療檢測基因臨床應用結(jié)果

搖床大鼠攜帶自然發(fā)生的突變，導致進行性共濟失調(diào)，其特征是浦肯野細胞 (PC) 丟失。我們之前曾報道過將搖床軌跡精細映射到大鼠 X 染色體的長臂。在這項工作中，我們試圖確定振動器表型背后的突變基因，并通過功能互補確認其身份。我們對候選區(qū)域進行了精細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) 啟動子生成了一種將 Slc9a6 表達靶向 PC 的腺相關病毒 (AAV)。我們通過腦室內(nèi)注射在 PC 變性開始之前管理 AAV，發(fā)現(xiàn)它減少了振動器電機、分子和細胞表型。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)生與革命國際數(shù)據(jù)庫描述：

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.