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首页> 外文期刊>Investigative ophthalmology & visual science >Mutational Analysis of MIR184 in Sporadic Keratoconus and Myopia
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Mutational Analysis of MIR184 in Sporadic Keratoconus and Myopia

机译：散发性圆锥角膜和近视眼中MIR184的突变分析

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Purpose.: A mutation miR-184(+57CT) in the seed region of miR-184 (encoded by MIR184 [MIM*613146]) results in familial severe keratoconus combined with early-onset anterior polar cataract and endothelial dystrophy, iris hypoplasia, congenital cataract, and stromal thinning (EDICT) syndrome (MIM#614303). In order to investigate the phenotypic spectrum resulting from MIR184 mutation, MIR184 was sequenced in a keratoconus cohort of mixed ethnicity and a Chinese axial myopia cohort. Methods.: Sequencing of MIR184 was performed in 780 unrelated keratoconus patients and 96 unrelated Han southern Chinese subjects with axial myopia. Effects of identified mutations on RNA secondary structure were predicted computationally using mFold and RNAFold algorithms. MIR184 amplicons from patients harboring mutations were cloned and transfected into human embryonic kidney 293T (HEK293T) cells, and mature mutant miR-184 expression was analyzed by stem-loop real-time quantitative PCR (RT-qPCR). Results.: Two novel heterozygous substitution mutations in MIR184 were identified in the two patients with isolated keratoconus: miR-184(+8CA) and miR-184(+3AG). Computational modeling predicted that these mutations would alter the miR-184 stem-loop stability and secondary structure. Ex vivo miR-184 expression analysis demonstrated that miR-184(+8CA) almost completely repressed the expression of miR-184 (P = 0.022), and miR-184(+3AG) reduced the expression of miR-184 by approximately 40% (P = 0.002). There was no significant association of rs41280052, which lies within the stem-loop of miR-184, with keratoconus. No MIR184 mutations were detected in the axial myopia cohort. Conclusions.: Two novel heterozygous substitution mutations in MIR184 were identified in two patients with isolated keratoconus: miR-184(+8CA) and miR-184(+3AG). Mutations in MIR184 are a rare cause of keratoconus and were found in 2 of 780 (0.25%) cases.
机译：目的：miR-184种子区中的miR-184（+ 57C> T）突变（由MIR184 [MIM * 613146]编码）可导致家族性严重圆锥角膜合并早期发作的前极性白内障和内皮营养不良，虹膜发育不全，先天性白内障和基质变薄（EDICT）综合征（MIM＃614303）。为了研究由MIR184突变产生的表型谱，在混合种族的圆锥角膜队列和中国轴向近视队列中对MIR184进行了测序。方法：对780例无亲缘性圆锥角膜患者和96例无亲缘性汉族眼轴性近视患者进行MIR184测序。使用mFold和RNAFold算法以计算方式预测鉴定出的突变对RNA二级结构的影响。将携带突变的患者的MIR184扩增子克隆并转染到人胚肾293T（HEK293T）细胞中，并通过茎环实时定量PCR（RT-qPCR）分析成熟突变体miR-184的表达。结果：在两名孤立圆锥角膜患者中，发现了MIR184中的两个新的杂合取代突变：miR-184（+ 8C> A）和miR-184（+ 3A> G）。计算模型预测这些突变将改变miR-184茎环稳定性和二级结构。离体miR-184表达分析表明，miR-184（+ 8C> A）几乎完全抑制了miR-184的表达（P = 0.022），而miR-184（+ 3A> G）降低了miR-184的表达减少约40％（P = 0.002）。在miR-184茎环内的rs41280052与圆锥角膜之间无显着关联。在轴性近视人群中未检测到MIR184突变。结论：在两名孤立圆锥角膜患者中发现了两个新的MIR184杂合替换突变：miR-184（+ 8C> A）和miR-184（+ 3A> G）。 MIR184中的突变是圆锥角膜的罕见原因，在780个病例中有2个（0.25％）被发现。

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