Mutation of IPO13 causes recessive ocular coloboma, microphthalmia, and cataract.
Mutation of IPO13 causes recessive ocular coloboma, microphthalmia, and cataract.
复制标题
IPO13突变导致隐性眼部缺损、小眼症和白内障
DOI：
10.1038/s12276-018-0079-0
复制
发表时间：
2018-04-27
影响因子：
12.8
通讯作者：
Jin ZB
中科院分区：
文献类型：
--
作者：
Huang XF;Xiang L;Cheng W;Cheng FF;He KW;Zhang BW;Zheng SS;Han RY;Zheng YH;Xu XT;Yu HY;Zhuang W;Leung YF;Jin ZB
眼缺损是眼的发育性结构缺陷，通常以复杂的眼部异常发生。然而，其遗传病因学仍然在很大程度上未被探索。在这里，我们报告的鉴定突变（c.331C>T，p.R111C）的IPO13基因在一个近亲家庭与眼缺损，小眼球，白内障的全外显子组测序和纯合性定位相结合。IPO13编码一种重要蛋白B家族蛋白，已被证明与缺损和小眼球的发病机制有关。我们发现Ipo 13在小鼠的角膜、巩膜、透镜和视网膜中表达。此外，与健康个体中的表达相比，患者中Ipo13的mRNA表达水平显著降低。在斑马鱼中，吗啉代寡核苷酸诱导的ipo13敲低引起剂量依赖性小眼症和缺损，这与患者的眼部表型高度相似。此外，视觉运动反应和视动反应均严重受损。值得注意的是，这些眼表型在ipo13缺陷斑马鱼可以拯救显着全长ipo13 mRNA，这表明在斑马鱼中观察到的表型是由于ipo13功能不足。总之，我们的研究结果首次证明了IPO13在眼睛形态发生中的新作用，并且IPO13功能的丧失可能导致人类和斑马鱼的眼缺损，小眼和白内障。
Ocular coloboma is a developmental structural defect of the eye that often occurs as complex ocular anomalies. However, its genetic etiology remains largely unexplored. Here we report the identification of mutation (c.331C>T, p.R111C) in the IPO13 gene in a consanguineous family with ocular coloboma, microphthalmia, and cataract by a combination of whole-exome sequencing and homozygosity mapping. IPO13 encodes an importin-B family protein and has been proven to be associated with the pathogenesis of coloboma and microphthalmia. We found that Ipo13 was expressed in the cornea, sclera, lens, and retina in mice. Additionally, the mRNA expression level of Ipo13 decreased significantly in the patient compared with its expression in a healthy individual. Morpholino-oligonucleotide-induced knockdown of ipo13 in zebrafish caused dose-dependent microphthalmia and coloboma, which is highly similar to the ocular phenotypes in the patient. Moreover, both visual motor response and optokinetic response were impaired severely. Notably, these ocular phenotypes in ipo13-deficient zebrafish could be rescued remarkably by full-length ipo13 mRNA, suggesting that the phenotypes observed in zebrafish were due to insufficient ipo13 function. Altogether, our findings demonstrate, for the first time, a new role of IPO13 in eye morphogenesis and that loss of function of IPO13 could lead to ocular coloboma, microphthalmia, and cataract in humans and zebrafish.
登录
查看更多内容
揭开与单侧造口和视网膜菌的近亲家族的遗传原因：扩大RAX突变的表型变异性。
影响因子：
4.6
作者：
Huang XF;Huang ZQ;Lin D;Dai ML;Wang QF;Chen ZJ;Jin ZB;Wang Y
通讯作者：
Wang Y
影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
影响因子：
4.1
作者：
Hornby, SJ;Dandona, L;Gilbert, CE
通讯作者：
Gilbert, CE
下一代测序揭示了一大群遗传性视网膜营养不良患者的基因型-表型相关性和突变谱
影响因子：
8.8
作者：
Huang, Xiu-Feng;Huang, Fang;Jin, Zi-Bing
通讯作者：
Jin, Zi-Bing
影响因子：
30.8
作者：
Fantes, J;Ragge, NK;FitzPatrick, DR
通讯作者：
FitzPatrick, DR