Fuchs' Endothelial Corneal Dystrophy and RNA Foci in Patients With Myotonic Dystrophy.
Fuchs' Endothelial Corneal Dystrophy and RNA Foci in Patients With Myotonic Dystrophy.
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DOI：
10.1167/iovs.17-22350
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发表时间：
2017-09-01
影响因子：
4.4
通讯作者：
Gong X
中科院分区：
文献类型：
--
作者：
Mootha VV;Hansen B;Rong Z;Mammen PP;Zhou Z;Xing C;Gong X
Fuchs内皮性角膜营养不良(FECD)最常见的原因是TCF4内含子CTG重复扩增。扩增的CUG重复RNA与剪接因子-肌盲样1(MBNL1)共定位于内皮细胞核内，作为分子标志。强直性肌营养不良1型(DM1)是一种由DMPK 3‘-非翻译区CTG重复扩增引起的神经肌肉疾病。在这项研究中，我们检查了患有DM1的FECD受试者内皮细胞中的RNA-MBNL1焦点，检验了DM1患者有FECD风险的假设，并确定了FECD队列中TCF4和DMPK扩张的患病率。使用FISH，我们检测了患有DM1的FECD受试者内皮细胞中的核RNA-MBNL1焦点。我们使用裂隙灯和镜面显微镜连续检查了13名无血缘关系的DM1患者的FECD。我们用短串联重复序列和三重重复序列启动的聚合酶链式反应方法对317名先证者的FECD队列中的TCF4和DMPK重复序列进行了基因分型。我们在患有DM1的FECD患者的内皮细胞中检测到大量与MBNL1共定位的核RNA焦点。13例DM1患者中有6例(46%)有裂隙灯和镜检发现FECD，而患病率为4%(P=5.5×10-6)。正如预期的那样，317名FECD先证者中有222名(70%)患有TCF4扩张症，而一名受试者在没有事先诊断为DM1的情况下患有DMPK扩张症。我们的工作表明，DM1患者有患FECD的风险。DMPK突变导致FECD的遗传负担，但并不常见。我们建立了两个聚集在RNA-MBNL1病灶上的重复扩张性疾病与FECD之间的联系。
The most common cause of Fuchs' endothelial corneal dystrophy (FECD) is an intronic CTG repeat expansion in TCF4. Expanded CUG repeat RNA colocalize with splicing factor, muscleblind-like 1 (MBNL1), in nuclear foci in endothelium as a molecular hallmark. Myotonic dystrophy type 1 (DM1) is a neuromuscular disorder caused by a CTG repeat expansion in the 3′-untranslated region (UTR) of DMPK. In this study, we examine for RNA-MBNL1 foci in endothelial cells of FECD subjects with DM1, test the hypothesis that DM1 patients are at risk for FECD, and determine prevalence of TCF4 and DMPK expansions in a FECD cohort. Using FISH, we examined for nuclear RNA-MBNL1 foci in endothelial cells from FECD subjects with DM1. We examined 13 consecutive unrelated DM1 patients for FECD using slit-lamp and specular microscopy. We genotyped TCF4 and DMPK repeat polymorphisms in a FECD cohort of 317 probands using short-tandem repeat and triplet repeat-primed PCR assays. We detected abundant nuclear RNA foci colocalizing with MBNL1 in endothelial cells of FECD subjects with DM1. Six of thirteen DM1 patients (46%) had slit-lamp and specular microscopic findings of FECD, compared to 4% disease prevalence (P = 5.5 × 10-6 ). As expected, 222 out of 317 (70%) FECD probands harbored TCF4 expansion, while one subject harbored DMPK expansion without prior diagnosis of DM1. Our work suggests that DM1 patients are at risk for FECD. DMPK mutations contribute to the genetic burden of FECD but are uncommon. We establish a connection between two repeat expansion disorders converging upon RNA-MBNL1 foci and FECD.
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影响因子：
56.9
作者：
EPHRUSSI, A;CHURCH, GM;GILBERT, W
通讯作者：
GILBERT, W
影响因子：
3.4
作者：
Matthaei, Mario;Zhu, Angela Y.;Kallay, Laura;Eberhart, Charles G.;Cursiefen, Claus;Jun, Albert S.
通讯作者：
Jun, Albert S.
影响因子：
9.9
作者：
Arsenault, ME;Prévost, C;Mathieu, J
通讯作者：
Mathieu, J
影响因子：
2.8
作者：
Gattey, Devin;Zhu, Angela Y.;Jun, Albert S.
通讯作者：
Jun, Albert S.
影响因子：
56.9
作者：
MAHADEVAN, M;TSILFIDIS, C;KORNELUK, RG
通讯作者：
KORNELUK, RG