Twelve exonic variants in the SLC12A1 and CLCNKB genes alter RNA splicing in a minigene assay.
Twelve exonic variants in the SLC12A1 and CLCNKB genes alter RNA splicing in a minigene assay.
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SLC12A1 和 CLCNKB 基因中的 12 个外显子变异会改变小基因测定中的 RNA 剪接。
DOI：
10.3389/fgene.2022.961384
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发表时间：
2022
影响因子：
3.7
通讯作者：
Shao, Leping
中科院分区：
文献类型：
--
作者：
Xin, Qing;Liu, Qihua;Liu, Zhiying;Shi, Xiaomeng;Liu, Xuyan;Zhang, Ruixiao;Hong, Yefeng;Zhao, Xiangzhong;Shao, Leping
背景：巴特综合征是一种罕见的肾小管疾病，由SLC12A1、KCNJ1、CLCNKA、CLCNKB、BSND或MAGED2基因变异引起。越来越多的证据表明，许多外显子突变可以通过改变各种剪接调控信号而影响前mRNA的正常剪接，并诱导外显子跳跃。因此，这项研究的目的是获得与BS相关的外显子突变对前mRNA剪接的影响的新见解。方法：我们利用生物信息学程序分析了6个致病基因中描述的所有错义、无义和同义变异，并确定了可能促进微基因系统跳过外显子的候选突变。结果：在SLC12A1的14个候选变异中，有12个(c.728G>；A、C.735C>；G、c.904C>；T、c.905G>；A、c.1304C>；T、c.1493C>；T、c.2221A>；T)和CLCNKB(c.226C>；T、c.228A>；C、c.229G>；A、c.229G>；C、c.1979C>；A)能够诱导剪接改变。这些变异体不仅可以干扰外显子剪接增强子(ESES)，还可以产生新的外显子剪接抑制子(ESSS)，或干扰传统的剪接位点。结论：据我们所知，这是一项关于BS致病基因外显子变异前mRNA变化的综合性研究。我们的结果加强了在mRNA水平上评估外显子变异后果的必要性。
Background: Bartter syndrome (BS) is a rare renal tubular disease caused by gene variants in SLC12A1, KCNJ1, CLCNKA, CLCNKB, BSND or MAGED2 genes. There is growing evidence that many exonic mutations can affect the pre-mRNA normal splicing and induce exon skipping by altering various splicing regulatory signals. Therefore, the aim of this study was to gain new insights into the consequences of exonic mutations associated with BS on pre-mRNA splicing. Methods: We analyzed all the missense, nonsense and synonymous variants described in six pathogenic genes by bioinformatics programs and identified candidate mutations that may promote exon skipping through a minigene system. Results: Results of the study showed that 12 of 14 candidate variants distributed in SLC12A1 (c.728G>A, C.735C>G, c.904C>T, c.905G>A, c.1304C>T, c.1493C>T, c.2221A>T) and CLCNKB (c.226C>T, c.228A>C, c.229G>A, c.229G>C, c.1979C>A) were identified to induce splicing alterations. These variants may not only disrupt exonic splicing enhancers (ESEs) but also generate new exonic splicing silencers (ESSs), or disturb the classic splicing sites. Conclusion: To our knowledge, this is a comprehensive study regarding alterations in pre-mRNA of exonic variants in BS pathogenic genes. Our results reinforce the necessity of assessing the consequences of exonic variants at the mRNA level.
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影响因子：
3.9
作者：
Famiglietti, Maria Livia;Estreicher, Anne;Gos, Arnaud;Bolleman, Jerven;Gehant, Sebastien;Breuza, Lionel;Bridge, Alan;Poux, Sylvain;Redaschi, Nicole;Bougueleret, Lydie;Xenarios, Ioannis
通讯作者：
Xenarios, Ioannis
影响因子：
4.8
作者：
Chang, Yao-Fu;Chan, Wai-Kin;Wilkinson, Miles F.
通讯作者：
Wilkinson, Miles F.
影响因子：
11
作者：
Kemter E;Rathkolb B;Becker L;Bolle I;Busch DH;Dalke C;Elvert R;Favor J;Graw J;Hans W;Ivandic B;Kalaydjiev S;Klopstock T;Rácz I;Rozman J;Schrewe A;Schulz H;Zimmer A;Fuchs H;Gailus-Durner V;Hrabe de Angelis M;Wolf E;Aigner B
通讯作者：
Aigner B
DOI：
10.1007/s00467-019-04371-y
发表时间：
2020-10
期刊：
Pediatric nephrology (Berlin, Germany)
影响因子：
--
作者：
Besouw MTP;Kleta R;Bockenhauer D
通讯作者：
Bockenhauer D
影响因子：
--
作者：
Han Y;Lin Y;Sun Q;Wang S;Gao Y;Shao L
通讯作者：
Shao L