人SLC25A13基因内含子突变IVS6-11A>G导致转录子剪接异常  

The mutation of IVS6-11A > G within human SLC25A13 gene leads to abnormal transcriptional splicing

作　　者：陈君霖 李海清 刘妍霖 李冰肖[2] 张占会[2] CHEN Junlin;LI Haiqing;LIU Yanlin;LI Bingxiao;ZHANG Zhanhui(Biomedical Translational Research Institute,Jinan University,Guangzhou 510632 China;Clinical Medicine Research Institute,the First Affiliated Hospital,Jinan University,Guangzhou 510632 China)

机构地区：[1]暨南大学生物医学转化研究院,广东广州510632 [2]暨南大学附属第一医院临床医学研究院,广东广州510632

出　　处：《暨南大学学报（自然科学与医学版）》2018年第5期369-375,共7页Journal of Jinan University(Natural Science & Medicine Edition)

基　　金：国家自然科学基金项目(81670813);广东省自然科学基金项目(2016A 030313099)

摘　　要：目的:通过minigene剪接实验分析SLC25A13基因内含子突变IVS6-11A> G是否导致转录子剪接异常,并确定其剪接方式,进而明确其在Citrin缺陷病的致病性.方法:构建携带突变的目的片段外显子捕获载体,转染293T细胞后逆转录PCR扩增转录产物,测序并分析.结果:IVS6-11A> G突变导致SLC25A13基因内含子6的3'端10个碱基保留于转录子中,致蛋白翻译提前终止,Citrin蛋白功能丧失.结论:SLC25A13基因IVS6-11A> G突变为剪接突变,其剪接方式为可变3'剪接,该突变为Citrin缺陷病致病突变.Objective:To identify the aberrant splicing transcripts caused by the intron variation IVS6-11A>G(c.615-11A>G)of human SLC25A13 gene using the minigene splicing assay and investigate its splicing manner,and to further clarify its pathogenicity in Citrin deficiency.Methods:The exon trapping vector carrying the mutated objective gene segment was constructed and transfected into 293T cells,the transcriptional products of vector were amplified by reverse transcription PCR,and then sequenced and analyzed.Results:The mutation of IVS6-11A>G resulted in the 10 bases at 3′-end of intron 6 of SLC25A13 gene retained in the transcript,thus to cause premature termination of protein translation and corresponding function loss of Citrin protein.Conclusion:The intronic mutation of IVS6-11A>G within SLC25A13 gene is a splicing mutation with its splicing pattern altering to 3′splice site.The mutation is a pathogenetic mutation of Citrin deficiency.

关 键 词：SLC25A13基因 IVS6-11A>G minigene剪接 CITRIN缺陷病 

分 类 号：R394.3[医药卫生—医学遗传学]