首页 / 院系成果 / 成果详情页

Splicing analysis of rare/novel synonymous or intronic variants identified in ABCB11 heterozygotes presenting as progressive intrahepatic cholestasis with low -glutamyltransferase 期刊论文

编号：

050f6045-c8bb-4cd3-b860-e2650667ae07
作者：

Wang, NengLi(王能里)#^[1,3]Qiu, YiLing^[3];Guan, WenCai^[2];Li, Gang^[4];Lu, Yi^[3];Zhang, MeiHong(张梅虹)^[1]Luan, WeiSha^[1];Wang, JianShe*^[3]
语种：

English
期刊：

HEPATOLOGY RESEARCH ISSN：1386-6346 2018 年 48 卷 7 期 (574 - 584) ; JUN
收录：
关键词：

ABCB11 intronic variant minigene system pre-RNA splicing synonymous variant
摘要：

AimThe aim of this study was to analyze the pathogenicity of rare/novel synonymous or intronic variants identified in ABCB11 heterozygotes presenting as progressive intrahepatic cholestasis with low -glutamyltransferase. MethodsThe enrolled variants were identified in ABCB11 between October 2009 and June 2016. The effects on pre-RNA splicing were analyzed by in silico tools and minigene splicing assay. ResultsThere were three intronic (c.908+5G>A, c.2815-8A>G, and c.612-15_-6del10bp) and two synonymous (c.1809G>A, p.K603K and c.2418C>T, p.G806G) variants with unknown significance identified in ABCB11 of five ABCB11 heterozygotes. Parental studies were carried out for four patients, and revealed that the variants with unknown significance were compound heterozygous with other pathogenic variants. The five variants with unknown significance had minor allele frequency <0.1% or were absent from controls, and had positive prediction results by in silico tools. The effects on pre-RNA splicing were further confirmed by minigene splicing assay. c.908+5A caused abnormal splicing in at least 78.53.8% of products using a cryptic splice site (ss) 22nucleotides (nt) upstream of the wild-type (WT) 5ss. Seven nucleotides of intron 22 upstream of the WT 3'ss was retained for all products from c.2815-8G. c.612-15_-6del caused exon 8 skipping in 24.8 +/- 7.7% of products, and 55nt of exon 8 downstream of the WT 3ss removal in remaining products. c.1809A led to exon 15 skipping. c.2418T removed exon 20 and 62nt of exon 21 downstream of the WT 3ss by using a cryptic ss. ConclusionsWe successfully identified five pathogenic synonymous or intronic variants with some common features. These features might help to choose the right variant for further functional assay.
推荐引用方式
GB/T 7714：

Wang Neng-Li,Qiu Yi-Ling,Guan Wen-Cai, et al. Splicing analysis of rare/novel synonymous or intronic variants identified in ABCB11 heterozygotes presenting as progressive intrahepatic cholestasis with low -glutamyltransferase [J].HEPATOLOGY RESEARCH,2018,48(7):574-584.
APA：

Wang Neng-Li,Qiu Yi-Ling,Guan Wen-Cai,Li Gang,&Wang Jian-She.(2018).Splicing analysis of rare/novel synonymous or intronic variants identified in ABCB11 heterozygotes presenting as progressive intrahepatic cholestasis with low -glutamyltransferase .HEPATOLOGY RESEARCH,48(7):574-584.
MLA：

Wang Neng-Li, et al. "Splicing analysis of rare/novel synonymous or intronic variants identified in ABCB11 heterozygotes presenting as progressive intrahepatic cholestasis with low -glutamyltransferase" .HEPATOLOGY RESEARCH 48,7(2018):574-584.
条目包含文件：

文件类型：PDF,文件大小：

正在加载全文

未找到全文

浏览次数：5  下载次数：0

分享到：

浏览次数：5

下载次数：0

打印次数：0