Three novel variants identified within ECM-related genes in Chinese Han keratoconus patients
Three novel variants identified within ECM-related genes in Chinese Han keratoconus patients
复制标题
中国汉族圆锥角膜患者 ECM 相关基因中发现的三种新变异
DOI：
10.1038/s41598-020-62572-0
复制
发表时间：
2020-04
影响因子：
4.6
通讯作者：
Shentu Xingchao
中科院分区：
文献类型：
--
作者：
Xu Xiayan;Zhang Xin;Cui Yilei;Yang Hao;Ping Xiyuan;Wu Jing;Yu Xiaoning;Jin Xiuming;Huang Xiaodan;Shentu Xingchao
圆锥角膜作为角膜移植的主要适应症，其发病机制至今仍不清楚。为了确定细胞外基质（ECM）相关基因的突变是否与中国汉族散发圆锥角膜（KC）患者有关，我们共招募了153名参与者，其中包括53名KC患者和100名健康对照。采用下一代测序和桑格测序技术对3个ECM相关基因（LOX、COL5A1和TIMP 3）进行突变分析。为了进一步证实三个ECM相关基因在圆锥角膜发病机制中的作用，我们在体外进行了实时定量PCR。结果显示，在KC患者的上述ECM相关基因中发现了3个新的序列变异（LOX中的c.95 G > A、COL5A1中的c.1372 C > T和TIMP3中的c.476 C > T），而在健康对照组中未发现。QPCR结果显示，KC患者中LOX和TIMP 3的表达水平降低，而COL5A1的表达水平无明显差异。这是第一次使用新一代测序技术在中国圆锥角膜患者中筛选如此多的ECM相关基因。我们发现了许多潜在的因果变异，扩大了许多突变谱，从而为其他研究人员提供了复制和进一步研究的新位点。
As the primary indication for corneal transplantation, the pathogenesis of keratoconus remains elusive. Aiming to identify whether any mutation from extracellular-matrix (ECM)-related genes contributes to the patients with sporadic cases of keratoconus (KC) from Chinese Han population, one hundred and fifty-three participants in total were enrolled in our study, including fifty-three KC patients and one hundred healthy controls. Mutational analysis of three ECM-related genes (LOX,COL5A1andTIMP3) with next-generation sequencing and Sanger sequencing was performed. To further confirm the function of three ECM-related genes in the pathogenesis of keratoconus, we performed Real-time Quantitative PCRin vitro. Results showed that three new sequence variants (c.95 G > A inLOX, c.1372 C > T inCOL5A1and c.476 C > T inTIMP3) were identified in aforementioned ECM-related genes in KC patients without being detected among the healthy controls. According to the results of QPCR, we found that the expression levels ofLOXandTIMP3were decreased in the KC patients, whileCOL5A1showed no significant difference of expression. This is the first time to screen so many ECM-related genes in Chinese keratoconus patients using next-generation sequencing. We find numerous underlying causal variants, enlarging lots of mutation spectrums and thus providing new sites for other investigators to replicate and for further research.
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影响因子：
2.2
作者：
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通讯作者：
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