TSPAN12 基因突变导致家族性渗出性玻璃体视网膜病变。

IF 3.8 3区 医学 Q2 GENETICS & HEREDITY
Yuqiao Ju, Tianhui Chen, Lu Ruan, Ye Zhao, Qing Chang, Xin Huang
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引用次数: 0

摘要

背景:报告新发现的TSPAN12突变与一种独特形式的家族性渗出性玻璃体视网膜病变(FEVR),并找出TSPAN12中重复出现的新型内含子变异导致FEVR的可能机制:结果:通过基于面板的 NGS 检测发现了九个 TSPAN12 突变,这些突变具有 FEVR 的独特形式。MINI-Gene 检测显示 mRNA 有两种剪接模式,分别处理 A 和 B 两条不同的带,突变型显示出 Exon11 跳接的剪接模式。在构建野生型和突变型 TSPAN12 载体时,发现出现了过早终止密码子(PTC)。体外表达检测显示,与野生型相比,转染突变型载体的细胞中 TSPAN12 mRNA 和蛋白质的表达水平明显下调。相反,翻译抑制剂CHX和UPF1小干扰RNA(si-UPF1)能显著提高转染突变载体的细胞中TSPAN12 mRNA或蛋白的表达量:在9例FEVR患者中,TSPAN12基因出现了9个突变,并伴有一系列独特的眼部异常。三例新型 TSPAN12 基因突变引发的 NMD 将导致参与微纤维生物合成和组装的 TSPAN12 蛋白减少,从而可能导致 FEVR,并提示内含子序列分析可能是遗传咨询和产前诊断的重要工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mutations in TSPAN12 gene causing familial exudative vitreoretinopathy.

Background: To report newly found TSPAN12 mutations with a unique form of familial exudative vitreoretinopathy (FEVR) and find out the possible mechanism of a repeated novel intronic variant in TSPAN12 led to FEVR.

Results: Nine TSPAN12 mutations with a unique form of FEVR were detected by panel-based NGS. MINI-Gene assay showed two splicing modes of mRNA that process two different bands A and B, and mutant-type shows replacement with the splicing mode of Exon11 hopping. Construction of wild-type and mutant TSPAN12 vector showed the appearance of premature termination codons (PTC). In vitro expression detection showed significant down-regulated expression level of TSPAN12 mRNAs and proteins in cells transfected with mutant vectors compared with in wild-type group. On the contrary, translation inhibitor CHX and small interfering RNA of UPF1 (si-UPF1) significantly increased mRNA or protein expression of TSPAN12 in cells transfected with the mutant vectors.

Conclusions: Nine mutations in TSPAN12 gene are reported in 9 FEVR patients with a unique series of ocular abnormalities. The three novel TSPAN12 mutations trigger NMD would cause the decrease of TSPAN12 proteins that participate in biosynthesis and assembly of microfibers, which might lead to FEVR, and suggest that intronic sequence analysis might be a vital tool for genetic counseling and prenatal diagnoses.

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来源期刊
Human Genomics
Human Genomics GENETICS & HEREDITY-
CiteScore
6.00
自引率
2.20%
发文量
55
审稿时长
11 weeks
期刊介绍: Human Genomics is a peer-reviewed, open access, online journal that focuses on the application of genomic analysis in all aspects of human health and disease, as well as genomic analysis of drug efficacy and safety, and comparative genomics. Topics covered by the journal include, but are not limited to: pharmacogenomics, genome-wide association studies, genome-wide sequencing, exome sequencing, next-generation deep-sequencing, functional genomics, epigenomics, translational genomics, expression profiling, proteomics, bioinformatics, animal models, statistical genetics, genetic epidemiology, human population genetics and comparative genomics.
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