Mutation Screening in the miR-183/96/182 Cluster in Patients With Inherited Retinal Dystrophy.
Mutation Screening in the miR-183/96/182 Cluster in Patients With Inherited Retinal Dystrophy.
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DOI：
10.3389/fcell.2020.619641
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发表时间：
2020
影响因子：
5.5
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Xu S;Coku A;Muraleedharan CK;Harajli A;Mishulin E;Dahabra C;Choi J;Garcia WJ;Webb K;Birch D;Goetz K;Li W
遗传性视网膜营养不良（IRD）是一种异质性致盲眼病，影响超过20万美国人和全球数百万人。到目前为止，已经确定了270个蛋白质编码基因在有缺陷时会导致IRD。然而，只有一种microRNA（miRNA），miR-204，已被报道负责IRD时，在其种子序列中发生点突变。以前，我们发现一个保守的，多顺反子，旁系同源的miRNA簇，miR-183/96/182簇，在所有的光感受器和其他感觉器官中高度特异性表达;在小鼠中该簇的失活导致多感觉缺陷综合征IRD。我们假设人类miR-183/96/182簇中的突变导致IRD。为了验证这一假设，我们在>1000例患有各种形式IRD的患者的外周血DNA样本中进行了前miR-183、-96、-182的突变筛查。我们鉴定了六种序列变体，三种在pre-miR-182中，三种在pre-miR-96中。这些变异存在于pre-miRNA-182或-96中，但不存在于成熟的miRNA中，并且不太可能是这些患者中IRD的原因。尽管如此，这些序列变体在pre-miRNAs中的性质和位置表明，一些可能对miR-182或miR-96的生物发生和成熟具有影响，并在疾病易感性中具有潜在作用。尽管到目前为止报告了阴性结果，但我们的研究建立了一个用于人类miR-183/96/182簇突变筛查的系统，以继续努力解开并更深入地了解miR-183/96/182簇在人类疾病中的潜在作用。
Inherited retinal dystrophy (IRD) is a heterogenous blinding eye disease and affects more than 200,000 Americans and millions worldwide. By far, 270 protein-coding genes have been identified to cause IRD when defective. However, only one microRNA (miRNA), miR-204, has been reported to be responsible for IRD when a point-mutation occurs in its seed sequence. Previously, we identified that a conserved, polycistronic, paralogous miRNA cluster, the miR-183/96/182 cluster, is highly specifically expressed in all photoreceptors and other sensory organs; inactivation of this cluster in mice resulted in syndromic IRD with multi-sensory defects. We hypothesized that mutations in the miR-183/96/182 cluster in human cause IRD. To test this hypothesis, we perform mutation screening in the pre-miR-183, -96, -182 in >1000 peripheral blood DNA samples of patients with various forms of IRD. We identified six sequence variants, three in pre-miR-182 and three in pre-miR-96. These variants are in the pre-miRNA-182 or -96, but not in the mature miRNAs, and are unlikely to be the cause of the IRD in these patients. In spite of this, the nature and location of these sequence variants in the pre-miRNAs suggest that some may have impact on the biogenesis and maturation of miR-182 or miR-96 and potential roles in the susceptibility to diseases. Although reporting on negative results so far, our study established a system for mutation screening in the miR-183/96/182 cluster in human for a continued effort to unravel and provides deeper insight into the potential roles of miR-183/96/182 cluster in human diseases.
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影响因子：
64.8
作者：
Denli, AM;Tops, BBJ;Hannon, GJ
通讯作者：
Hannon, GJ
影响因子：
10.5
作者：
Han, JJ;Lee, Y;Kim, VN
通讯作者：
Kim, VN
影响因子：
64.5
作者：
Grishok, A;Pasquinelli, AE;Mello, CC
通讯作者：
Mello, CC
DOI：
10.1073/pnas.1401464112
发表时间：
2015-06-23
影响因子：
11.1
作者：
Conte, Ivan;Hadfield, Kristen D.;Black, Graeme C. M.
通讯作者：
Black, Graeme C. M.
影响因子：
64.5
作者：
Auyeung VC;Ulitsky I;McGeary SE;Bartel DP
通讯作者：
Bartel DP